We investigated a possible association between CASP-10 gene polymorphisms and susceptibility to cancer through a meta-analysis. Eight studies with a total of 29,936 cancer cases and 34,041 healthy controls were included. Meta-analysis results showed that the rs13006529 T carrier was significantly associated with increased cancer risk (OR = 1.17, 95%CI = 1.01-1.36, P = 0.03). However, rs3900115 and rs13010627 showed no association with cancer susceptibility (all P > 0.05). In the subgroup analysis by cancer type, we found that the rs13006529 T carrier was a risk factor for breast cancer (OR = 1.17, 95%CI = 1.01-1.36, P = 0.03). Similarly, no association was found between CASP-10 polymorphisms and susceptibility to lymphoma, myeloma, melanoma, or lung cancer (all P > 0.05). This meta-analysis suggests that the rs13006529 T carrier in the CASP-10 gene might be a risk factor for cancer susceptibility, especially for breast cancer.