Objective: Perineural invasion in oral squamous cell carcinoma is an ominous process enabling tumor cells spread through and along nerves. This study was performed to highlight the frequency of perineural invasion in oral squamous cell carcinoma using immunohistochemical aid in addition to the evaluation of the role of galanin in this process. Methods: Total 54 paraffin-embedded tissue blocks of radical resections of oral squamous cell carcinoma were evaluated for perineural invasion both histopathologically and immunohistochemically using Protein Gene Product 9.5 with the assessment of the role of galanin in this process. Results: About 22 cases showed perineural invasion in histopathological sections that were elevated to 41 upon staining with Protein Gene Product 9.5. In histopathological sections, the largest nerve diameter showed perineural invasion was significantly correlated with a tumor depth of invasion (p=0.025), however, this correlation was non-significant in Protein Gene Product 9.5 immunostained sections (p=0.203). Perineural invasion status in both hitopathological and Protein Gene Product 9.5 immunostained sections showed no significant association in regard to tumor grade and stage (p=0.848, p=0.520) for histopathological, and (p=0.238, p=0.216) for Protein Gene Product 9.5 immunostained sections, respectively. Galanin expression showed no significant association with perineural invasion status in histopathological sections, however, this association was significant in Protein Gene Product 9.5 sections (p=0.180, p=0.027) respectively. Conclusions: Perineural invasion can dramatically be elevated using immunohistochemical aid, by which it may accentuate the role of galanin as a neuropeptide involved in perineural invasion in oral squamous cell carcinoma.