Published data on the association between FAS -1,377 G/A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 studies including 10,564 cases and 12,075 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with AA variant genotype when all the eligible studies were pooled into the meta-analysis (for AA vs GG: OR = 1.19; 95% CI = 1.01-1.40; P (heterogeneity) = 0.05; for recessive model: OR = 1.21; 95% CI = 1.04-1.41; P (heterogeneity) = 0.05). In the subgroup analysis by ethnicity, borderline statistically significantly increased risks were found among Asians for recessive model (OR = 1.20; 95% CI = 1.00-1.45; P (heterogeneity) = 0.01). In the subgroup analysis by population-based controls or hospital-based controls, statistically significantly increased risks were found among groups with population-based controls for AA versus GG (OR = 1.27; 95% CI = 1.02-1.58; P (heterogeneity) = 0.05) and recessive model (OR = 1.25; 95% CI = 1.00-1.59; P (heterogeneity) = 0.01). For breast cancer, borderline statistically significantly increased risks were found for AA versus GG (OR = 1.29; 95% CI = 1.00-1.67; P (heterogeneity) = 0.41). In summary, this meta-analysis suggests that the FAS -1,377 G/A polymorphism is associated with cancer susceptibility.