Objective Head and neck cancer (HNC) patients have a high incidence of cancer-related posttraumatic stress disorder (PTSD) and other anxiety and depressive disorders. We report the results from the first pilot randomized controlled trial in which the efficacy of an early cognitive-behavioral therapy (CBT) program was compared with a non-directive supportive counseling (SC) intervention in reducing PTSD, general anxiety and depressive symptoms, and improving perceived quality of life in newly diagnosed, distressed HNC patients undergoing radiotherapy. Patients and methods Thirty-five HNC patients (mean age = 54.8 years; 80% males) with elevated levels of PTSD, depression or anxiety were randomized to seven individual sessions of a multi-modal CBT or non-directive SC, concurrent with patients' radiotherapy. The SC intervention provided non-directive counseling support. PTSD, anxiety and depressive symptoms (primary outcomes), and cancer-related appraisals and quality of life (secondary outcomes) were assessed pre-intervention (baseline), 1 month, 6 months and 12 months post-intervention by diagnostic clinical interviews and validated self-report questionnaires. Results The CBT and SC interventions were found to be equal in their effects in reducing PTSD and anxiety symptoms both in the short and longer term. However, up to 67% of patients in the CBT program no longer met clinical or sub-clinical PTSD, anxiety and/or depression by 12 months post-treatment compared with 25% of patients who received SC. Conclusion Findings indicate that the early provision of psychotherapy has utility in reducing PTSD, anxiety and depressive symptoms, and preventing chronic psychopathology in distressed HNC patients.