Objectives The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among never-smokers / drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socioeconomic impact of premature mortality from OSCC. We attempted to study these differences and quantify their economic impact with a health economic analysis. Materials and Methods A health economic analysis using population-level data was conducted in Singapore and India. The cost of premature mortality and Years of Potential Productive Life Lost (YPPLL) were derived with the Human Capital Approach. Results In the Singapore cohort, the cost of premature mortality was US $66,636,560, and 1826 YPPLL from OSCC. In India, this was US $3,626,594,997, and 8,990,200 YPPLL. Conclusion Young-onset OSCC is an aggressive disease. The socioeconomic costs from premature mortality are substantial. With the growing incidence of OSCC, further studies are needed to elucidate the genetic basis and role of treatment escalation to improve prognosis.