Objective To analyze differential proteins under high-glucose culture conditions using liquid chromatography-mass spectrometry and bioinformatics,and to explore the common pathways leading to the development of diabetes and liver cancer in this environment.Methods Using quantitative proteomics,high-throughput gene chips,and unlabeled quantitative mass spectrometry analysis,we compared the differential expression of protein peptides in liver cancer cells under high glucose and conventional culture conditions,screened for differentially expressed proteins,and performed differential protein enrichment analysis.Utilize the gene expression matrix of liver cancer in the TCGA database for subsequent analysis of differentially expressed genes.Results Differential proteins were mainly enriched in the expression of metabolic related signaling pathways.Under high glucose cultivation conditions,liver cancer cells might promote tumor growth and proliferation through active lipid metabolism reprogramming.Through screening of differentially expressed proteins by LC-MS/MS,it was found that COMMD9 is highly expressed in a high glucose environment.Through analysis of the TCGA database,it was also confirmed that COMMD9 is highly expressed in liver cancer tissues,and COMMD9 and T staging can serve as independent risk factors for the prognosis of liver cancer.Conclusion By means of LC-MS and bioinformatics analysis,it is found that the high expression of COMMD9 in high glucose environment can promote the proliferation and metabolic reprogramming of liver cancer cells,and affect the prognosis of liver cancer patients.COMMD9 is expected to become a potential therapeutic target for liver cancer with diabetes.