Our current systemic review and meta-analysis mainly focussed on associations between HMGB1 rs1045411, rs1360485, rs1412125, or rs2249825 polymorphisms and cancer susceptibility, we went further by conducting subgroup analysis based on cancer type and ethnic groups of subjects, and revealed no statistical differences between rs1045411 polymorphism and cancer risk amongst LC, OSCC, HCC, CRC, and UCC. This evidence concerns the gene HMGB1 and cancer.