Although some epidemiological studies have investigated the association between Hepatitis C virus (HCV) infection and the development of kidney cancer, the results are far from consistent. We conducted a systematic review and meta-analysis of observational studies to determine the association. PubMed, EMBASE and Cochrane database were searched from January 1, 1975 to January 7, 2020. Study selection, data extraction and bias assessment (using the Newcastle-Ottawa scale) were performed independently by 2 authors. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated using a random-effects model. In all, 16 studies (11 cohort studies and 5 case-control studies) involving a total of 391,071 HCV patients and 38,333,839 non-HCV controls were included. The overall analysis showed a 47% higher risk to develop kidney cancer among the patients with HCV infection (pooled OR 1.47; 95% CI 1.14-1.91), despite significant heterogeneity (I = 87.6%); The multivariable meta-regression showed that study design, age, sample size, and HIV coinfection were significant sources of variance, and totally accounted for 82% of the I . The risk of KC in HCV patients was further increased in studies without HCV/HBV- and HCV/HIV- co-infection (pooled OR 1.66; 95%CI 1.23-2.24). Multiple sensitivity analyses did not change the significant association. The present meta-analysis indicated that HCV infected patients have a significantly higher risk of developing kidney cancer. Our results highlighted the rationale for improved renal surveillance in HCV patients for the early diagnosis of kidney cancer. Further investigations for the mechanisms underlying HCV-induced kidney cancer are warranted.This article is protected by copyright. All rights reserved.