Through multiple bioinformatics methods, we analyzed the data from Oncomine, TCGA, CCLE, HPA, DNMIVD, and cBioPortal database to explore the potential underlying carcinogenic effect of COL5A1, including the relevance of COL5A1 to the outcome, DNA methylation, tumor microenvironment, immune cells infiltration, and drug sensitivity in 33 human cancers. The gene discussed is COL5A1; the disease is cancer.