Objective To investigate SLC35D1 expression regulated by DNA methylation and its relationship with prognosis in patients with colon adenocarcinoma.Methods The expression and methylation data of colon adenocarcinoma were downloaded from The Cancer Genome Atlas(TCGA)database to analyze the expression and methylation of SLC35D1 in colon adenocarcinoma tissues and normal tissues,and the expression and methylation data of colon adenocarcinoma were down-loaded from the comprehensive gene expression database for verification.The prognostic value of SLC35D1 in colon adenocar-cinoma was analyzed by Kaplan-Meier method.The nomogram model of patients was constructed,and functional enrichment analysis of SLC35D1 and co-expressed genes was performed.The relationship between SLC35D1 expression and tumor-infiltrating immune cells was analyzed and the relationship between SLC35D1 promoter methylation and transcriptional silen-cing was verified.Results The expression of SLC35D1 in colon adenocarcinoma tissues was lower than that in normal tissues(P<0.01).The methylation of SLC35D1 in colon adenocarcinoma tissues was higher than that in normal tissues(P<0.01).The overall survival rate of patients with low SLC35D1 expression was lower than that with high SLC35D1 expression(P<0.05).The nomogram model constructed by the combination of SLC35D1 expression,age,and TNM staging could effectively predict the prognosis of patients with colon adenocarcinoma.The change of SLC35D1 expression level was related to tumor im-mune microenvironment.Quantitative PCR(qRCP)results showed that SLC35D1 expression was low in colon adenocarcinoma/colorectal cell SW480,and SLC35D1 expression was recovered after treatment with DNA methyltransferase inhibitors(P<0.05).Conclusion The low expression of SLC35D1 in colon adenocarcinoma is regulated by its methylation and is a marker of poor prognosis in patients.It may regulate the progression of colon adenocarcinoma through MAPK pathway and influence of the tumor immune microenvironment.