Epidemiological studies have demonstrated close associations between SET8 rs16917496 T/C polymorphism and cancer risk, but the results of published studies were not consistent. We therefore performed this meta-analysis to explore the associations between rs16917496 T/C polymorphism and cancer risk. Five online databases were searched. Odds ratios (ORs) with a 95% confidence interval (CI) were calculated to assess the association between rs16917496 T/C polymorphism and cancer risk. In addition, heterogeneity, accumulative, sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 13 publications involving 5878 subjects were identified according to included criteria. No significant cancer risk was observed in genetic model of SET8 rs16917496 T/C polymorphism in Asian populations (C vs. T: OR = 1.04, 95%CI = 0.88–1.23, P = 0.63%; TC vs. TT: OR = 1.17, 95%CI = 0.96–1.24, P = 0.11%; CC vs. TT: OR = 0.90, 95%CI = 0.60–1.37, P = 0.63; TC+CC vs. TT: OR = 1.11, 95%CI = 0.90–1.38, P = 0.33; CC vs. TT+TC: OR = 0.92, 95%CI = 0.65–1.30, P = 0.63). Furthermore, similar associations were found in the subgroup analysis of race diversity, control design, genotyping methods, and different cancer types. In summary, our meta-analysis indicated that the SET8 rs16917496 T/C polymorphism may not play a critical role in cancer development in Asian populations.