X-ray cross-complementing group 6 (XRCC6) plays an important role in the DNA double-strand breaks repair and the maintenance of genomic integrity. XRCC6 C1310G polymorphism may be involved in the development of cancer through increasing genomic damages. However, studies investigating the relationship between XRCC6 C1310G polymorphism and cancer risk yielded contradictory results. To shed some light on these inconsistent findings, a meta-analysis was performed to clarify the effect of XRCC6 C1310G polymorphism on the susceptibility of cancer. A systemic literature search of PubMed, EMBASE, and China National Knowledge Infrastructure databases was conducted from their inception to September 26, 2012. The association between XRCC6 C1310G and cancer risk was assessed by the pooled odds ratio (OR) with 95 % confidence intervals (95 % CI) calculated by meta-analysis. A total of 15 eligible studies (4,642 cancer cases and 6,059 controls) were identified. Overall, there was obvious evidence for an association between XRCC6 C1310G polymorphism and increased risk of cancer under two genetic comparisons (GG vs. CC: fixed-effect OR 1.35, 95 % CI 1.10-1.66, I (2) = 17.0 %; GG vs. CG/CC: fixed-effect OR 1.25, 95 % CI 1.02-1.53, I (2) = 0.0 %). Subgroup analysis indicated that the association was significant in Asians (G vs. C: random-effect OR 1.13, 95 % CI 1.01-1.26, I (2) = 51.3 %; GG vs. CC: fixed-effect OR 1.43, 95 % CI 1.14-1.81, I (2) = 0.0 %; GG vs. CG/CC: fixed-effect OR 1.37, 95 % CI 1.09-1.72, I (2) = 0.0 %), but not in Europeans. Data from the current meta-analysis support the existence of an association between XRCC6 C1310G polymorphism and cancer risk in Asians. Studies with larger sample size are needed to further evaluate the influence of XRCC6 C1310G polymorphism on susceptibility of various cancers.