Background: Our study aimed to evaluate the clinical utility of detecting plasma microRNAs (miR-21 & miR-92a) for diagnosis of colorectal cancer patients and its relation to tumor staging. Patients and Methods: Quantitative real-time RT-PCR was applied to determine the relative expression level of miR-21 and miR-92a in serum. The sensitivity and specificity of these markers were evaluated by receiver operating characteristic (ROC) curve analysis. Final staging of colorectal cancer cases was assigned according to results of histopathologic examination of surgically resected specimens. Results: This study included 52 cases of colorectal cancer (CRC), 20 cases of precancerous colorectal lesions, and 20 healthy controls. Both Plasma miR-21 and Plasma miR-92a were significantly higher in CRC group compared to both the control group and precancerous group. Also, they were significantly higher in advanced CRC stages than early CRC stages. The sensitivity and specificity of miR-21 for discriminating CRC from controls were found to be 90.38% and 100.0%, respectively. However, for miR-92a, sensitivity and specificity were found to be 94.23% and 100.0%, respectively. For discriminating CRC cases from precancerous lesions, the sensitivity and specificity of miR-21 were found to be 75.08% and 95.0%, respectively. However, for miR-92a, sensitivity and specificity were found to be 80.77% and 100.0%, respectively. Conclusions: both plasma miR-21 and miR-92a have significant value for early detection of CRC as non-invasive screening molecular biomarkers with high sensitivity and specificity. They also help for differentiation between patients with benign and malignant colorectal lesions and those with early and advanced CRC.