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. Here, GADD45G is linked to malignant colon neoplasm.