Oral squamous cell carcinoma is associated with severe morbidity, recurrence of tumor, and reduced survival rate despite advances in treatment. Perineural invasion (PNI) is associated with neurotropic malignancy. PNI is due to the tropism of cancer cells toward nerve bundles in tissue. The aim of this literature review is to study the definition, patterns of PNI, Prognostic and therapeutic significance, and mechanism of PNI along with a molecular insight into oral cavity squamous cell carcinoma. Liebig type A pattern defines PNI as the presence of tumor cells within the peripheral nerve sheath & infiltration into the epineurium, perineurium, or endoneurium. Liebig type B pattern defines PNI as a tumor encircling at least 33% of a nerve. Few studies demonstrated an association between PNI and cervical metastasis which indicate poor prognosis. A higher level of expression of nerve growth factor and tyrosine kinase is associated with PNI in OSCC which can be considered as a biomarker of PNI. PNI needs to be studied in detail as it is associated with the aggressiveness of the tumor and decreased survival.