The breakthrough of key core technologies is a major issue that China encounters at the current stage of its develop-ment.The reasons why key core technologies are difficult to conquer,not superficially because of a comprehensive technology blockade from the developed countries,but fundamentally because of some systematic problems,including that the basic research support is insufficient;the collaborations between industry,academia and research departments are not close enough;the early market is difficult to form;and the institutional mechanism of developing key core technologies is not valid enough,and so on.Therefore,to make a breakthrough in key core technologies is not simply a technological issue,but a systemic issue.According-ly,this study explored the breakthrough mechanism of key core technologies in the context of innovation ecosystem evolution.As for research methods,this study explored the key core technology breakthrough mechanism by applying the exploratory dual case study method,and taking the high-end scientific instrument industry as the research subject.Two typical cases of Illumina and BGI have been selected as the samples of international leading firm and the domestic catch-up firm for a comparative analysis of the gene sequencer technology breakthroughs.The research steps are as follows:(1)The authors of this paper obtained the first-hand data and second-hand data through interviews and other means,analyzed and summarized the characteristics of research objects,e-vent sequences,influential events,environment,organization and other factors related to time and order with the help of time axis,and divided the innovation ecosystem evolution process from the start-up stage to the prosperity stage;(2)Based on the literature re-search,we established a theoretical analysis framework by measuring three categories,including system structure,dynamic capabilities and value proposition,to provide guidance for data coding;(3)We also processed the open coding,axial coding and selective coding in the proceduralised grounded analysis,and made the theoretical saturation achieved when there is no new property of category identi-fied;(4)We finally conducted a comparative analysis of two cases by vertical and horizontal comparison.The research results are as following:(1)The innovation ecosystem is the carrier for the breakthrough of key core technolo-gy,and the innovation ecosystem promotes the key core technology breakthroughs through the evolution process of"individual re-production,population shaping and community integration";(2)International leading firms tend to choose the maintenance breakthrough path of"product-service-ecology",while the domestic firms tend to choose the reverse breakthrough path of"service-product-ecology";(3)The implementation of the key core technology breakthroughs by domestic firms usually goes through three main stages.The first stage is to develop their own innovation ecosystem within the innovation ecosystem of interna-tional leading firms.The second stage is to withdraw from the constraints of the innovation ecosystem of international leading firms and implement reverse breakthroughs upstream of the industrial chain after a critical event occurs.The third stage is to purpose-fully carry out ecological innovation around key core technologies,forming confrontation with international leading firms;and(4)The key core technology breakthrough process of domestic firms is often affected by four important factors,including value propo-sition,innovation environment,dynamic capability,and critical events.This study revealed the interactional relationships be-tween the evolution of innovation ecosystem and the breakthroughs of key core technologies,which brings enlightenment to gov-ernment policy-making and enterprise innovation practice.This study have put forward the following suggestions:(1)The government should focus on optimizing the policy system,provi-ding comprehensive policy supports to enterprises with the potential to make breakthroughs in key core technologies,and establish a suitable policy environment for cultivating an innovation ecosystem conducive to key core technology breakthroughs,such as promoting the first set of policies,implementing application benchmarks,industrial demonstration,and scenario development projects.(2)For the catch-up firms,it is important to recognize that the key core technology breakthrough process of the latecomers is different from the one of international leading firms.Domestic catch-up firms may follow the reverse breakthrough path of"service-product-ecol-ogy"to develop the key core technologies.In this process,domestic firms should attach importance to establishing correct value propo-sitions,improving dynamic capabilities,and keenly paying attention to the impact of critical events.