Published data regarding the association between the cytosolic serine hydroxymethyltransferase (SHMT1) C1420T (Leu474Phe) polymorphism and solid tumor risk have shown inconclusive results. To derive a more precise estimation of the relationship, we performed a meta-analysis of 23 published studies that included 14,409 cancer cases and 16,996 controls. A comprehensive search was conducted to identify all eligible studies of the SHMT1 rs1979277 polymorphism and solid tumor risk. The pooled odds ratios (ORs) and the 95% confidence intervals (95%CIs) were calculated using a fixed- or random-effects model. Heterogeneity was represented by PH; publication bias and sensitivity analysis were also explored. Overall, no significant associations were found for any genetic models tested. However, upon stratification by cancer type, a significant decreased risk of breast cancer risk was identified in the homozygote comparison (OR = 0.79, 95%CI = 0.65-0.97 for TT versus CC). An analysis stratified by ethnicity and source of controls revealed an obvious decrease in risk among Asian groups in all genetic models, and among population-based controls only in the homozygote comparison and recessive model. Therefore, our meta-analysis suggested that the SHMT1 C1420T polymorphism was associated with decreased risk of breast cancer. Significant protective effects were found among Asian populations, but not in Caucasian groups. Due to some minor limitations, our findings should be confirmed by further studies.