Abstract Background Postoperative chemotherapy is an essential treatment in locally advanced colon cancer, however, effective biomarkers for predicting patients who will benefit from this therapy are lacking. This study aims to explore the clinical value of protein arginine methyltransferase 5 (PRMT5) in guiding adjuvant chemotherapy in patients with colon cancer. Methods PRMT5 expression was determined via immunohistochemistry (IHC) in tumor and paratumor samples from 199 colon cancer patients who underwent radical surgery. The correlation between PRMT5 expression and clinicopathological parameters, as well as clinical outcomes, was subsequently investigated. Results The protein expression levels of PRMT5 were significantly elevated in colon cancer tissues compared to paratumor tissues (P