BACKGROUND: MicroRNAs (miRNAs) play pivotal roles in post-transcriptional regulation of gene expression and have emerged as crucial regulators in cancer development, progression, and metastasis. This study aimed to assess the expression profiles of miR-23, miR-223, miR-1246, and miR-150 in serum samples obtained from colorectal cancer (CRC) patients before and three months after surgery, in comparison to a healthy control group, to explore their biomarker potential. METHODS: A total of 50 blood samples were collected from patients with CRC (pre- and post-surgery), along with 50 samples from healthy controls. The relative expression levels of miR-23, miR-223, miR-1246, and miR-150 in the serum were quantified using quantitative real-time PCR. RESULTS: Our findings revealed upregulated expression levels of miR-23, miR-1246, and miR-223, while miR-150 exhibited significant downregulation in the serum of CRC subjects compared to healthy controls. Receiver operating characteristic (ROC) analysis indicated that miR-23 and miR-150 could distinguish CRC cases from controls with relatively high accuracy. Moreover, three months post-surgery, miR-23, miR-1246, and miR-223 serum levels were downregulated, and miR-150 was significantly upregulated. However, no significant correlations were observed between serum levels of the studied genes and the clinical features of our patients. CONCLUSIONS: The serum levels of miR-23 and miR-150 hold promise as potential biomarkers for the diagnosis and prognosis of CRC.