Abstract Background We translated and validated the Urdu version of the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire’s Head and Neck (H&N) Cancer Module (EORTC QLQ-H&N35) and assessed its convergent and discriminant validity by examining correlations of QoL with depression, anxiety, and resilience. Methods We translated the EORTC QLQ-H&N35 according to EORTC instructions. Patients at a tertiary care hospital in Pakistan completed a survey consisting of Urdu versions of EORTC QLQ-C30 (core QoL tool), QLQ-H&N35, Hospital Anxiety and Depression Scale, and Wagnild and Young Resilience Scale (RS-14). Content validity, convergent validity, discriminant validity, and reliability (using Cronbach’s alpha) of the EORTC QLQ-H&N35 were assessed. Results Our sample comprised 250 patients with H&N cancer, most commonly oral (82%). The Urdu translations were comprehensible for all patients. The Cronbach alpha for QLQ-H&N35 multi-item domains ranged from 0.75 to 0.98 (acceptable to excellent), barring “Senses Problems”, which was less than the generally acceptable level (0.50). The patient-reported content validity index (CVI) scores for relevance and clarity of the Urdu version of the QLQ-H&N35 were 0.93 and 0.92, respectively (both excellent). Our results revealed weak bidirectional correlations of the QLQ-H&N35 with resilience, depression, and anxiety, showing good discriminant validity. A weak-to-moderate but significant negative correlation (r: − 0.185 to − 0.613; p