Purpose: Previous studies of MMP-3-1171 5A/6A in cancers haveproduced inconclusive outcomes. This updated meta-analysis wasperformed to clarify the link between this variant and cancer. Methods: Databases including PubMed, Google Scholar, EMBASEand Cochrane were searched for data collection. The associations were calculated by odds ratios with 95% CIs. Results: 63 eligible studies with 14,252 cases and 15,176 controls were included. The codominant2, codominant3, dominant, recessiveand allelemodels were found to be significantly associated with 1.28-, 1.13-, 1.13-, 1.19- and 1.13-foldenhanced overall risk of cancer, respectively. Stratification analysis revealed a 1.28-times enhanced risk of esophageal cancer(codominant1), 1.29- and 1.26-fold(codominant3)and 1.18- and 1.28-fold(recessivemodel)enhanced risk in colorectal and gastrointestinal cancers, respectively, 1.30-, 1.35- and 1.22-times in codominant model1, dominant and allele models for breast cancer, 1.56-fold(codominant2) for gynecological cancer and2.40-times in codominant model2 for hepatocellular cancer. Conclusion: This meta-analysis suggests a significant association between theMMP-3-1171 5A/6A variant and cancer. This meta-analysis was registered at INPLASY (registration number: INPLASY202280049).