Introduction <p>Oral squamous cell carcinoma is the most prevalent of all the oral cancers. There is no definitive marker available for its early diagnosis and its effective prognosis. YAP serves as a transcriptional regulator in hippo tumor suppressor pathway thereby activating the transcription of genes taking part in cellular proliferation, alteration, migration, and invasion. On the contrary, PARK2 acts as a tumor suppressor and has been widely explored in various malignancies. However, its role in OSCC carcinogenesis is untrodden.</p> Aim <p>To evaluate the Immunohistochemical expression of YAP and PARK2 in oral epithelial dysplasia and Oral Squamous Cell Carcinoma and establish them as prognostic markers.</p> Material and Method <p>The study sample consisted of 70 formalin fixed paraffin embedded tissue sections of normal oral mucosa (10), oral epithelial dysplasia (30) and oral squamous cell carcinoma (30). Immunohistochemical analysis of YAP and PARK2 was done and final scores were calculated. Further, the markers were graded as low and high expression groups. Statistical analysis was done using chi-square test, cox regression analysis and Spearman’s correlation. Kaplan Meier plot for survival analysis was also plotted.</p> Result <p>Immunohistochemical expression of YAP depicted a gradual incline from normal oral mucosa to oral squamous cell carcinoma while PARK2 showed a reverse trend. Significant difference of YAP and PARK2 expression between three groups was noted. Inverse moderate degree of correlation was observed between both the markers in OSCC group.</p> Conclusion <p>Concomitant immunoexpression of YAP and PARK2 with a moderate degree of inverse correlation from normal oral mucosa to oral squamous cell carcinoma could probably serve as diagnostic and prognostic markers as they might act through a common mechanism, probably hippo/YAP signaling, which could be further confirmed by larger sample size, including longer follow up in future studies.</p>