Background: Oral cancer is one of the most prevalent cancers worldwide, with squamous cell carcinomas being the most common type, accounting for 90% of all oral cancers with high recurrence in many cases. Thus, the development of new methods to predict the prognosis of OSCC is essential. Aim: To investigate and correlate the expression profile of miR-34c using RT-qPCR and quantify CD68 antibody usingimmunohistochemistry in normal oral mucosal tissues versus different grades of OSCC.Methodology: Cases of oral squamous cell carcinomas were retrieved from archival blocks between 2016 to 2021, from the Department of Oral and Maxillofacial Pathology, Faculty of dentistry.Results: All grades of OSCC revealed significant lower mean expression of miR-34c in comparison to normal mucosal tissue samples at p-value (0.000) with the lowest expression noticed in well differentiated OSCC at p-value (0.000).CD68+ Macrophages in each group of OSCC were found to be significantly higher compared to the normal oral mucosa with the highest expression seen at (Well- Moderate group) at p-value of (0.000).