The association between B-cell lymphoma 2 (Bcl-2) polymorphism and cancer is under debate and remains elusive. This meta-analysis was performed to evaluate the relationships of Bcl-2 -938 C>A polymorphism (rs2279115) with susceptibility and prognosis of cancer. Odds ratios (ORs) were used to measure the association between Bcl-2 polymorphisms and cancer risk. Hazard ratios (HRs) were used to measure the association between Bcl-2 polymorphisms and cancer prognosis. On the basis of 26 studies about Bcl-2 -938C>A polymorphism and cancer, we found Bcl-2 -938 C>A polymorphism was significantly associated with increased cancer risk in dominant model (OR = 1.12, 95%CI: 1.00-1.25, P = 0.04), recessive model (OR = 1.38, 95%CI: 1.11-1.71, P = 0.004), allelic model (OR = 1.15, 95%CI: 1.04-1.28, P = 0.007) and homozygote comparison(OR = 1.44, 95%CI: 1.11-1.87, P = 0.006). Furthermore, Bcl-2 -938 C>A polymorphism was significantly associated with increased cancer risk in Asians but not in Caucasians. Moreover, Bcl-2 -938 C>A polymorphism was not significantly associated with the prognosis of cancer (AA vs CA: OR = 0.99, 95%CI: 0.77-1.27, P = 0.93; AA vs CC: OR = 0.92, 95%CI: 0.65-1.30, P = 0.63; AC vs CC: OR = 0.94, 95%CI: 0.80-1.11, P = 0.48; CC vs AA+CA: OR = 1.21, 95%CI: 0.69-2.13, P = 0.50; AA vs CC+CA: OR = 0.99, 95%CI: 0.48-2.04, P = 0.97). Studies with larger samples and gene-environment interactions are needed to validate our findings.