Clear cell renal cell carcinoma (CCRCC) is the most common subtype of renal cell cancer and accounts for 70 % of renal cell cancer. CCRCC remains an enigmatic tumor type, as the molecular genetic mechanisms are still unclear. MicroRNA (miR) 149 functions as a tumor suppressor and plays an important role in the carcinogenesis of renal cells. In this study, we enrolled 1,000 CCRCC patients and 1,000 cancer-free controls to evaluate the association of miR149 rs71428439 with the risk of CCRCC by a case-control study to determine the effects on CCRCC risk. miR149 rs71428439 was significantly associated with increased CCRCC risk (odds ratio (OR) for trend = 1.53, P for trend = 4.04 × 10(-11)), with ORs (95 % confidence intervals (CIs)) of 1.42 (1.17-1.72) associated with AG genotype and 2.27 (1.76-2.94) associated with GG genotype, compared with subjects with AA genotype. The expression levels of miR149 in cancer tissues were significantly lower than those in adjacent normal tissues (P = 0.005), and per G allele has significantly lower miR149 levels in both tumor tissues and adjacent normal tissues. Our data suggest that the GG genotypes of miR149 rs71428439 predispose their carriers to CCRCC, and miR149 rs71428439 may be a new biomarker for predicting the risk of CCRCC.