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Purpose: Perineural invasion (PNI) is associated with poor prognosis in a variety of cancers. Our aim was to determine the clinicopathological factors associated with PNI in colorectal cancer (CRC) and its impact on patient survival. Material and methods: The clinical data of 1412 patients diagnosed with CRC from July 2013 to July 2016 were retrospectively collected. PNI was determined based on hematoxylin-eosin staining. The relationships of PNI with various clinicopathological factors and prognosis were analyzed. Results: The incidence of PNI in the entire cohort was 21.5%. PNI was significantly more common in patients with lower tumor differentiation, higher tumor stage, vascular invasion, TNM stage, tumor diameter, MMR/KRAS/NRAS/BRAF mutation, and more positive lymph nodes. Logistic regression analysis showed that T stage, vascular invasion, tumor diameter, and MMR were the main influencing factors of PNI. Cox regression analysis showed that poor tumor differentiation, N stage, TNM stage, PNI, and BRAF status were independent prognostic factors for OS. The OS, CSS, and PFS rate of the PNI (−) group was higher than that of the PNI (+) group, and the difference was statistically significant (P < 0.001). Conclusion: PNI in patients with colorectal cancer is significantly associated with T stage, TNM stage, vessel invasion, tumor diameter, MMR status, and BRAF mutation. PNI status is an independent prognostic factor for CRC. Assessing the postoperative PNI status may help predict prognosis and determine further treatment options for these patients. [ABSTRACT FROM AUTHOR]