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Background: Standard outcome disease parameters like tumor control, overall survival and complications are now complemented with health-related quality of life (HRQoL) data as an important source of information concerning the impacts of disease and treatment outcomes for head and neck cancer patients. Aim: This study aims to assess changes in oral cancer patients' HRQoL and the impact of disease stage on HRQoL scores from the point of diagnosis (pretreatment) through the one, three and six month follow-ups. Differences in characteristics between patients presenting early and late were also explored. Methods: HRQoL data were collected from seven hospital-based centers using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) V4.0. A total of 300 patients were recruited. Independent sample t-test, χ2 and paired sample t-test were used to analyze data. The Statistical Package for Social Sciences (SPSS) version 12.0 was used, whereby P < 0.05 was considered to be statistically significant. Results: Mean age was 61.0 ± 13.7 years old with most of them being females (60.7%) and of Indian ethnicity (35.0%). Betel quid chewing was the most common risk habit practiced (48.2%). The most common subsite was tongue and floor of mouth (42.6%). Surgical intervention (41.1%) was the most common treatment. Significant differences in ethnicity and treatment modality were observed between early and late stage patients. Among late stage patients, attrition rate increased significantly with increasing age, with higher proportions of attrition at later follow-ups. At pretreatment, HRQoL scores were significantly lower for late than early stage patients. At one month posttreatment, GF, H&N domains and FACT-H&N (TOI) summary scores showed significant deterioration among both early and late stage patients. In contrast, emotional domain showed significant improvement for early and late stage patients at 1, 3 and six month posttreatment. Although HRQoL deterioration was still observed among early and late stage patients at six months posttreatment, it did not achieve statistical significance. Conclusion: Advanced disease is associated with poorer HRQoL. Domains most commonly affected were the functional, physical and head and neck concerns. Although ethnic differences were observed across different disease stages, its influence on patients' HRQoL was not evident in this study.