Advanced cancer patients experience stress and are at risk for developing psychological problems. Early diagnosis and suitable intervention are very important for their quality of life and compliance with chemotherapy. The Hospital Anxiety and Depression Scale (HADS) is one of the most commonly used mood scales; however, HADS has not been validated for use with cancer patients undergoing chemotherapy. The purpose of this study was to validate HADS as a screening tool for psychological distress among cancer patients undergoing chemotherapy. We also identified possible factors contributing to psychological distress and explored the development of original screening tools. Fifty subjects agreed to complete HADS and consult with psychiatric specialists. Possible contributing factors to psychological distress were identified by HADS and logistic regression analysis. The mean score for patients with psychological distress was 20.0 ± 8.93, and for patients without distress was 9.67 ± 6.11; scores for patients with psychological distress were significantly higher. The optimal cutoff point of psychological distress appeared to be 17. This cutoff point was associated with 72.7% sensitivity and 82.1% specificity. The factor “recurrent cancer” (p=0.043) had an odds ratio of 7.24 (1.21-61.2). We verified that HADS is a useful screening tool for cancer patients undergoing chemotherapy. The factor “recurrent cancer” was shown to contribute to psychological distress. Palliat Care Res 2011; 6(2): 150-157