ObjectiveTo review the impact of perineural invasion (PNI) on the occurrence, development, and prognosis of colorectal cancer (CRC), providing a reference for the diagnosis and treatment of CRC. MethodThe latest literature relevant researches on the mechanism, diagnosis, treatment, and prognosis of PNI in CRC both domestically and internationally was reviewed. ResultsThe current studies revealed that the mechanisms underlying PNI involved nerve growth factors, chemokines, and other signaling molecules, which regulated the interactions between the nerves and cancer cells, promoting the tumor invasion and metastasis. The diagnostic approaches primarily relied on the histopathological examination, with immunohistochemistry, and radiomics enhancing detection accuracy. Therapeutically, the PNI-positive patients benefited from surgical intervention in combination with neoadjuvant or adjuvant treatments. The FOLFOX regimen markedly improved disease-free survival. Targeting neural pathways and immune checkpoint inhibitors (such as programmed cell death 1 and cytotoxic T lymphocyte associated protein 4 inhibitors) showed potentials in reducing neural invasion and tumor progression. Emerging strategies that disrupted tumor-nerve interactions also represented promising therapeutic avenues. PNI was recognized as a critical prognostic indicator for CRC, providing guidance in risk assessment and individualized treatment planning. ConclusionsPNI serves as an important indicator for evaluating the prognosis of CRC, it has a guiding value for therapy decision-making. Further research of molecular mechanisms and diagnostic methods relevant PNI can potentially yield more effective therapeutic options and is expected to improve prognosis of patients with CRC.