MicroRNAs (miRNAs) have emerged as essential gene expression regulators associated with human diseases such as colorectal cancer (CRC). The purpose of this study was to evaluate the expression of miR-330-3p and its target gene BMI1 in tissue samples of patients with CRC, polyp, and healthy adjacent tissue samples and their association with clinicopathological and demographic factors such as age,tumor stage, grade, and lymph node invasion of the tumor. Following the extraction of total RNA from approximately 50 mg of colon and rectum tissue of 82 patients with CRC, 13 polypoid lesions, and 26 marginal healthy tissues using RiboEx reagent, cDNA synthesis was performed, and then quantitative real-time PCR was used to detect the expression levels of miR-330-3p and BMI1. Alterations in the gene expression were assessed using the 2(-∆∆ CT) method. The expression of miR-330-3p in all of the CRC samples was significantly lower than in adjacent healthytissues and polyp (P<0.001). BMI1 was up-regulated in 97.9% of CRC tissue compared to healthy adjacent tissues and polyps (P<0.001). A negative reverse correlation between the miR-330-3p and BMI1 gene was observed in the CRC samples (r= -0.882, P<0.001). Down-regulation of miR-330-3p and BMI1 overexpression strongly correlates with higher tumor stage and lymph node invasion.The AUC for miR-330-3p and BMI1expression was 0.982 (sensitivity, 98.5%; specificity, 78.8%), and 0.971 (sensitivity, 97.6%; specificity, 84.6%) (P<0.001), respectively. Our results indicated that miR-330-3p and BMI1 expression probably could be considered potential diagnostic or prognostic biomarkers for CRC patient.