In summary, we found that shikonin suppresses colon cancer cell proliferation and migration through cellular experiments and identified eight genes (CCNB3, IL-1α, CXCL8, CDKN2A, MYC, IGFBP3, SQSTM1, and GADD45G) associated with cell senescence through systematic bioinformatics analysis. This evidence concerns the gene SQSTM1 and colonic neoplasm.