MicroRNAs, a novel class of small noncoding RNAs, are key players in many cellular processes, including cell proliferation, differentiation, invasion and regeneration. Tissue and circulatory microRNAs could serve as useful clinical biomarkers and deregulated expression levels have been observed in various cancers. Gene variants may alter microRNA processing and maturation. Thus, we aimed to investigate the association of MIR196a2 rs11614913 (C/T), MIR499a rs3746444 (A/G) polymorphisms and their combination with cancer susceptibility in an Egyptian population. Sixty five renal cell carcinoma (RCC) and 60 hepatocellular carcinoma (HCC) patients and 150 controls were enrolled in the study. They were genotyped using realtime polymerase chain reaction technology. Both miR196a2*T and miR499a*G were associated with RCC risk, but only miR196a*T was associated with HCC development. Carriage of the homozygote combinations (MIR196a2*TT + MIR499a*AA) and (MIR196a2*CC + MIR499a*GG) was associated with 25 and 48 fold elevation of likelhood to develop RCC, respectively. The miR196a2 SNP was also linked with larger tumor size in RCC and advanced tumor stage in HCC. miR196a2 and miR499a combined genotypes were associated with RCC and HCC. Further functional analysis of SNPs is required to confirm relationships between genotypes and phenotypes.