Many studies have reported the relationship between CXCL12 G801A polymorphism and cancer risk, with conflicting results. In this study, we tried to clarify the possibility that this polymorphism may increase cancer risk by conducting an updated meta-analysis. PubMed and EMbase were searched for case-control studies regarding the association of the gene polymorphism and cancer risk. Data were extracted and odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of the association. Heterogeneity among articles and publication bias was also assessed. Significantly increased risk for cancer was found (A vs. G: OR=1.26, 95% CI=1.13-1.40, P < 0.01; AA+AG vs. GG: OR=1.33, 95% CI=1.16-1.52, P < 0.01). In subgroup analysis, statistically elevated cancer risk was found in both Asian and Caucasian populations (for Asian, AA+AG vs. GG: OR=1.74, 95% CI=1.22-2.47, P < 0.01; for Caucasian, AA+AG vs. GG: OR=1.24, 95% CI=1.09-1.42, P < 0.01). Our result indicated that CXCL12 G801A polymorphism is a risk factor for cancer. To validate the finding, further large-size case-control studies are warranted.