One of the highly prevalent cancers worldwide is Colorectal cancer (CRC). MicroRNAs (miRNAs) are small non-coding molecules. A candidate miRNA whose expression was correlated with tumor aggressiveness and poor prognosis in colon cancer patients is miR-223. Furthermore, miR-223 could be used as a diagnostic marker for CRC and a therapeutic target as well. The present study aimed to examine the potential of miR-223 to diagnose CRC in Egyptian patients and correlate its level with carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19-9), and different stages of colon cancer. The study included 60 individuals selected from the National Oncology Institute; the subjects were classified into two groups: 20 healthy control group volunteers and 40 colon cancer patients group, which were subdivided into 3 sub-groups according to severity: Low-risk colon cancer group which included stages (zero-one): 15 subjects, Intermediate-risk colon cancer group which includes stage (two): 13 subjects and High-risk colon cancer group which includes stages (three-four): 12 subjects Evaluation of serum levels of CEA and CA 19.9 was done through sandwich ELISA and miR-223 was done through RT-PCR. There was a significant increase in miR-223 expression levels in patient groups compared to the control group. There was a strong positive significant correlation between the expression levels of miR-223 and different degrees of risk. Moreover, the serum levels of miR-223 had an Area under the Curve (AUC) value of 0.997, with 100% sensitivity and specificity of 90% at p<0.05. Thus, miR-223 could be used as a diagnostic and prognostic marker in CRC.