A meta-analysis incorporating 34 case-control studies from 19 articles involving 12,197 cases and 13,488controls was conducted to assess the effects of three genetic variants of Toll-like receptor 9 (TLR9): rs187084,rs352140, and rs5743836. Studies on associations between TLR9 polymorphisms and cancer risk weresystematically searched in electronic databases. The reported odds ratios (OR) and 95% confidence intervals(CI) were pooled to assess the strength of any associations. The results showed that the rs187084 polymorphismwas significantly associated with an increased risk of cancer (CC vs TC+TT: OR=1.14, 95% CI=1.02-1.28),specifically cervical cancer (C vs T: OR=1.19, 95% CI=1.05-1.34; TC vs TT: OR=1.32, 95% CI=1.10-1.58; CCvs TT: OR=1.31, 95% CI= 1.03-1.68; CC+TC vs TT: OR=1.32, 95% CI=1.11-1.56), and that this association wassignificantly positive in Caucasians (CC vs. TC+TT: OR=1.18, 95% CI=1.01-1.38). The rs352140 polymorphismhad a protective effect on breast cancer (GA vs GG: OR=0.77, 95% CI=0.66-0.89), whereas the rs5743836polymorphism was likely protective for digestive system cancers (CC+TC vs TT: OR=0.81, 95% CI=0.66-0.98).In conclusion, our results suggest that the rs187084 polymorphism may be associated with an elevated cancerrisk, whereas polymorphisms of rs352140 and rs5743836 may play protective roles in the development of breastand digestive system cancers, respectively. From the results of this meta-analysis further large-scale case-controlstudies are warranted to verify associations between TLR9 polymorphisms and cancer.