Introduction: Oral squamous cell carcinoma (OSCC) of oral cavity is more complex with multi step progression which involves combination of acquired and inherited alterations in DNA sequence. Deregulated proliferation of cancer cells with altered energy metabolism and glucose is the main source of energy which converts to lactate even under highly aerobic conditions is hall mark of cancer. Cancer cells have high gluttony towards lipids and cholesterol for carcinogenic process including cell growth, cell migration and metastasis formation. Aim: To find out the role of Apoproteins, lactate, lipoproteins, magnesium, glucose, glycosylated hemoglobin in OSCC.Materials and methods: Blood samples were collected from 68 subjects (34 OSCC subjects and 34 age and gender matched healthy subjects) from R.L.Jalappa Hospital and Research Centre, Kolar, Karnataka, India. The biochemical parameters were analyzed by using dry chemistry fully automated VITROS 5.1 FS analyzer. Glycosylated haemoglobin (HbA1C) was analyzed by Bio- Rad D10. Statistical analysis was done by using institutional licensed version of IBM SPSS 20. Results: Significant reduction in plasma glucose, serum magnesium with significant increase in serum lactate levels in OSCC were observed compared to healthy subjects. There was no significant change in HbA1C. Total cholesterol, triglycerides, LDL and Apo A were significantly decreased in patients. No significant alteration in HDL and Apo B was noted in OSCC patients. Conclusion: Reprogrammed energy metabolism in cancer cells with significant elevation of serum lactic acid levels with significant reduction of plasma glucose and serum magnesium levels strongly suggest cancer aggravation which promotes angiogenesis. Disruption of lipid metabolic pathways and lipid homeostasis play an important role in progression of cancer. These abnormal levels of lactate and lipids are associated with poor progression of OSCC.