In the last decade there has been an increasing awareness about ‘quality of life’ (QOL) of cancer survivors in developing countries. The study aimed to cross-culturally adapt and validate the FACT-H&N (v4) in Urdu language for Pakistani head and neck cancer patients. In this study the ‘same language adaptation method’ was used. Cognitive debriefing through in-depth interviews of 25 patients to assess semantic, operational and conceptual equivalence was done. The validation phase included 50 patients to evaluate the psychometric properties. The translated FACT-H&N was easily comprehended (100%). Cronbach’s alpha for FACT-G subscales ranged from 0.726 e 0.969. The head and neck subscale and Pakistani questions subscale showed low internal consistency (0.426 and 0.541 respectively). Instrument demonstrated known-group validity in differentiating patients of different clinical stages, treatment status and tumor sites (p < 0.05). Most FACT summary scales correlated strongly with each other (r > 0.75) and showed convergent validity (r > 0.90), with little discriminant validity. Factor analysis revealed 6 factors explaining 85.1% of the total variance with very good (>0.8) Kaiser-Meyer-Olkin and highly significant Bartlett’s Test of Sphericity (p < 0.001). The cross-culturally adapted FACT-H&N into Urdu language showed adequate reliability and validity to be incorporated in Pakistani clinical settings for head and neck cancer patients.