Failure of apoptosis is one of the hallmarks of cancer. As an execution-phase caspase, caspase-9 plays a crucial role during apoptosis. To examine whether the Ex5+32 G>A (rs1052576) polymorphism in the CASP-9 gene alters cancer risk, we conducted a comprehensive meta-analysis of 7 case-control studies consisting of a total of 1668 cancer cases and 2294 healthy controls. All studies considered, A allele and A allele carriers of Ex5+32 G>A in the CASP-9 gene had significant associations with cancer risk (OR=0.72, 95% CI, 0.58-0.89, P= 0.003; OR= 0.76, 95% CI, 0.63-0.92, P= 0.004; respectively). In the subgroup analysis, we found that the A allele of Ex5+32 G>A was a protective factor for cancer risk in Chinese and American populations (OR=0.60, 95% CI, 0.44-0.81, P<0.001; OR= 0.80, 95% CI, 0.69-0.94, P= 0.005; respectively). Similarly, we also found positive associations between A allele carriers of Ex5+32 G>A and cancer risk in Chinese and American populations (OR=0.63, 95% CI, 0.44-0.90, P= 0.01; OR= 0.78, 95% CI, 0.62-0.98, P=0.03; respectively). In addition, we identified that A allele and A allele carriers of Ex5+32 G>A may decrease the risk of cancer in the Asian population (OR=0.60, 95% CI, 0.44-0.81, P<0.001; OR= 0.63, 95% CI, 0.44-0.90, P= 0.01; respectively). In conclusion, this meta-analysis demonstrated that A allele and A allele carriers of the Ex5+32 G>A polymorphism in the CASP-9 gene may be protective factors for cancer risk.