Purpose Health-related quality of life (HRQOL) has now become an important outcome measure in the assessment of patients treated for oral cancer. We summarize the influence of various factors in the treatment of oral cancer on HRQOL after surgery. Methods A review of the current literature was carried out. Results Site-specific assessment of HRQOL should be encouraged, rather than assessment of head and neck cancer as a whole. In general the long-term HRQOL of oral cancer patients seems good with HRQOL at 1 year being equivalent to long-term HRQOL. A number of different patient and treatment factors were identified that affect HRQOL. These include age, gender, site, stage, emotional status, smoking and alcohol, marital status and income, performance status, method of reconstruction, access, mandibular resection, neck dissection, percutaneous endoscopic gastrostomy, and post-operative radiotherapy. Conclusions HRQOL should be considered as part of the overall process of care for oral cancer patients.