Introduction: Understanding the prognostic factors and underlying biological mechanisms of oral cancer is essential for improving diagnostic accuracy and therapeutic outcomes. Inflammatory responses mediated by immune cells can have dual roles in tumor development, either inhibiting or promoting growth. C-reactive protein (CRP), has been identified as a potential biomarker for various cancers. Additionally, hematological parameters such as hemoglobin levels, red and white blood cell counts, and platelet indices are associated with cancer pathogenesis. Alterations in these parameters indicate systemic inflammation and immune system dysregulation, which can influence tumor dynamics and prognosis. Materials and Method: 50 patients of confirmed oral squamous cell carcinoma (OSCC), and 30 healthy individuals were considered. Fasting venous blood samples were obtained from all participants for biochemical assessment. The evaluation focused on various hematologic parameters, including hemoglobin concentration, red and white blood cell counts, platelet count, hematocrit, and additional related indices. Results: OSCC patients demonstrated notable elevations in inflammatory indicators and significant shifts in blood-based markers. Increased CRP levels and a higher neutrophil?to?lymphocyte ratio (NLR) correlated with more advanced disease and heavy tobacco use. Furthermore, variations in CRP, absolute counts of neutrophils and lymphocytes, and NLR were significantly associated with different histological grades of carcinoma. Conclusion: Elevated CRP levels were closely linked with inflammation and known risk factors such as tobacco use, while shifts in hematological markers like altered white and red blood cell counts and platelet indices—reflected systemic responses to tumor progression and immune activation in oral cancer patients.