<p>The X-ray repair cross-complementary group 1 (XRCC1) gene 399 codon polymorphism may alter the structure of DNA repair enzymes to regulate DNA repair capacity. Impaired DNA repair ability can lead to the development of cancers such as prostate cancer (PCa). Although the association between the XRCC1 codon 399 polymorphism and the risk of PCa has been widely reported, the results have not been clear. Data were collected from PubMed, EMBASE, the Wanfang Database, CNKI and the Web of Science. A total of 20 case‒control studies were selected for inclusion in this updated analysis to determine the association between the XRCC1 codon 399 polymorphism and the risk of PCa. The crude odds ratio (OR) and 95% confidence interval (CI) were calculated using Stata (version 18) software to evaluate the association between the XRCC1-Arg399Gln polymorphism and prostate cancer. We identified 20 eligible reports that included 5803 cases of prostate cancer and 5470 controls. Our meta-analysis revealed a significant association between the XRCC1-Arg399Gln polymorphism and the risk of prostate cancer. In particular, according to the recessive models, this polymorphism was associated with a significantly increased prevalence of prostate cancer in Asian populations (AA versus AG + GG: OR = 1.255, 95% CI = 1.063–1.481, <i>P</i> = 0.507, I², &lt; 25%). Based on these results, the XRCC1-Arg399Gln polymorphism may be a risk factor for prostate cancer and can be used as a biomarker to predict the prognosis of prostate cancer.</p>