Context The assessment of cancer-related symptoms requires culturally adapted and psychometrically validated symptom assessment tools. The M. D. Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) is a useful instrument for measuring symptom burden that was specifically developed for head and neck cancer patients. Objectives To validate the Spanish version of the MDASI-HN. Methods We evaluated the psychometric features of the MDASI-HN in patients with head and neck cancer. We evaluated the item-scale correlations and the internal consistency. We conducted principal axis factoring to identify the underlying dimensions as a measure of construct validity. The convergence/concurrent validity was assessed with the University of Washington Quality of Life Questionnaire for Head and Neck Patients, and known-group validity and test-retest reliability also were assessed. Results One hundred thirty patients were included. The mean ± SD age was 60.5 ± 13.6 years; 68% of patients were male, 42% had laryngeal tumors, and 45.9% had Stage III tumors. Forty-seven percent of the patients underwent surgery, 55% underwent radiotherapy, and 36% underwent chemotherapy. The global Cronbach alpha for the HN module was 0.81. The factor analysis identified two factors (Factor 1: speech, mucus, coughing, and constipation; Factor 2: teeth, taste, sores, swallowing, and skin). The correlation with the global score of the University of Washington Quality of Life was -0.68. The difference in the MDASI-HN scores according to Eastern Cooperative Oncology Group performance status was statistically significant (2.72 vs. 4.01, P = 0.006). The intraclass test-retest correlation was 0.62. Conclusion The Spanish version of the MDASI-HN is reliable and valid for evaluating cancer-related symptoms in head and neck cancer patients. © 2016 American Academy of Hospice and Palliative Medicine.