Background: Head and neck cancer (HNC) accounts for 5% of all new cancer cases and most were locally advanced. Positron emission tomography/computed tomography (PET/CT) in radiotherapy practice in locally advanced head and neck squamous cell carcinoma (HNSCC) is being used in staging and proper contouring. Proper staging is essential for accurate treatment decision. Methods: This is a prospective phase II study conducted as a single institute centre to evaluate the role of PET/CT-treatment in staging, contouring and response evaluation of 30 patients with locally advanced HNSCC in contrast to CT scan. Our cases did not undergo radical surgery for the primary tumour, and biopsy was taken with PET/CT post-treatment to evaluate response. Results: Median age of patients was 49·4 years (minimum age of 32 years and maximum of 68 years). Males were predominant 22 (73·3%). Nasopharynx was the predominant site 16/30 (53·3%). PET/CT changed the overall staging in 40% of the patients (upstaged in 36·7% and downstaged in 3·3%). Gross tumour volume (GTV) of PET/CT was smaller in 23 patients (76·7%) and larger in 5 (16·7%) than the GTV of conventional CT, whereas GTV of lymph nodes of PET/CT was larger in 20 patients (67·7%) and smaller in 4 (13·3%). PET/CT study detected bone metastasis in two nasopharyngeal carcinoma patients and two cases of 2nd primary tumours which were not detected using conventional CT. The Cox-regression model showed that the median standardised uptake volume (SUV) of the initial tumour had been a dependent predictor of death in patients with HNSCC (p-value = 0·033) where the risk of death was 0·725 times among patients with high SUV of the initial tumour. Consequently, the size of GTV of the tumour was significant in the prediction of death (p = 0·018). Conclusions: 18F-FDG-PET/CT is useful for staging, radiotherapy delineation as well as aiding proper decision making, in addition to assessment of treatment response in HNSCC patients.