The polymorphism rs2853669 within the promoter of telomerase reverse transcriptase gene (TERTp) has been debated about its role in cancer risk and prognosis. Additionally, several studies report inconsistent results concerning the modifying effect of rs2853669 on the prognostic value of TERTp mutations in cancer patients. Here, we performed this meta-analysis to comprehensively evaluate the role of rs2853669 in the risk and prognosis of human cancer, and further assess its modifying impact on TERTp mutations in the survival of cancer patients. We systematically searched literature via PubMed, Web of Science, and EMBASE through July 2016, and included 22 eligible studies. The overall analysis (64,119 cases and 78,988 controls) demonstrated that rs2853669 did not increase or decrease the overall cancer risk. Subsequent analyses also did not reveal any association between rs2853669 and overall cancer prognosis. However, we identified a modifying effect of rs2853669 on TERTp mutations in that, among cancer patients with TERTp mutations, only those carrying the TT genotype had a poor survival (Hazard ratio = 1.56, 95% confidence interval = 1.06-2.28); subgroup analyses by cancer type also supported these results. In conclusion, our findings suggest that rs2853669 could be important for assessing the prognostic value of TERTp mutations. Future large studies are required to further validate our results.