Background: Cancer patients are more susceptible to psychological issues such as nervousness, traumatic stress, and depression because their vulnerability to stress increases after a cancer diagnosis. Multiple harmful effects of psychological strain on health outcomes are possible. Those who have undergone surgery for cancer are more at risk of cancer-related fatigue and psychological distress. Studies in Western countries have shown a 40-80% reduction in cancer-related distress if the patients are subjected to appropriate psycho-oncological interventions.Objectives: The aims of this study were to: 1) screen head and neck cancer patients for distress using a cancer-specific questionnaire; 2) test the association of cancer-related distress with socio-demographic and clinical characteristics of patients; and 3) evaluate the effect of cognitive behavioral therapy (CBT) on the distress level of head and neck cancer patients about to undergo surgery. Materials and methods: A pre-tested, semi-structured, self-administered 23-item Questionnaire on Stress in Cancer patients (QSC-R23) was used to measure the level of distress. Three sessions of CBT of one hour duration on every alternate day have been given to elicit the response. Categorical data were analyzed using the Chi-square test. Pre and post-scores were compared using a paired sample t-test. The correlation was done to compare continuous variables using Pearson's correlation test. To determine how other related factors will affect the results, linear regression analysis was used.Results: The mean age of the 94 participants was 54.64 ± 10.97 years. The mean pre-score was 60.06 ± 20.42, and the post-score was 34.63 ± 5.3. There was a significant improvement in the post score (P-value = 0.0001) implying a reduction in stress among the study participants after the 3 sessions of CBT. Participants with middle/high monthly family income (P-value = 0.013, 95% CI= 0.639-17.418), no past medical history (P-value = 0.0001, 95% CI= 0.639-17.418), and no past psychiatric history (P-value = 0.008, 95% CI= 3.621-20.162) were statistically significantly affected by the difference in distress score. Conclusion: This study has successfully reported that CBT can reduce distress levels among cancer patients. However, there is still a need to explore this research and produce more relevant, evidence-based literature.