Objectives: RAD51 gene plays an important role in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN), colorectal cancer, ovarian cancer and acute leukaemia. A number of studies assessed the association between RAD51 135G/C polymorphism and the risk of these cancers in different population. However, the results have been inconclusive. We performed a systematic meta-analysis to evaluate the association between RAD51 135G/C polymorphism and the risk of these four types of cancer. Methods: Pubmed, Cochrane library and Chinese Biomedical Literature Database (CBM) were searched for case-control studies on RAD51 135G/C polymorphism and the risk of SCCHN, colorectal cancer, ovarian cancer and acute leukaemia published up to Oct 31, 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results: A total of twenty-two published studies, with 6836 cases and 8507 controls were included. Overall, no significant association was found between RAD51 135G/C polymorphism and the risk of the four types of cancers (G/G vs. C/C: OR = 0.83, 95% CI: 0.43-1.59, P = 0.57). However, there was a significant association between this polymorphism and SCCHN risk in the subgroup analysis by cancer type (G/G vs. C/C: OR = 2.46, 95% CI: 1.08-5.61, P = 0.03). Conclusion: The RAD51 135G/C polymorphism was associated with the risk of SCCHN.