Study Design A longitudinal single-arm cohort design. Background The Patient-Specific Functional Scale (PSFS) is among the most commonly used measures to assess physical function. Objectives We aimed to translate and cross-culturally validate PSFS to Nepali (PSFS-NP) and further assess its psychometric properties. Methods We translated and cross-culturally adapted the PSFS to Nepali (PSFS-NP) following recommended guidelines. We recruited 104 Nepalese with musculoskeletal pain to assess psychometric properties. We assessed internal consistency (Cronbach's alpha), two-week test-retest reliability (Intraclass Correlation Coefficient - ICC3,2), smallest detectable change at 90% confidence interval (SDC90) and construct validity. Concurrent validity was assessed against the Nepali versions of Oswestry Disability Index (ODI-NP), Global Rating of Change (GROC-NP), and Numerical Pain Rating Scale (NPRS-NP). Receiver Operating Characteristic (ROC) curves were plotted to assess responsiveness and area under the curve (AUC), and estimated the minimum important change (MIC). Results PSFS-NP showed good reliability with Cronbach's alpha = 0.75; ICC = 0.89 (95% CI: 0.78, 0.94) and SDC90 = 1.46. It demonstrated significant correlations with ODI-NP (r = -0.47, P = 0.001), GROC-NP (r = 0.71, P < 0.01), and NPRS-NP (rs = -0.32 and -0.55, P < 0.001). AUCs ranged between 0.72 to 0.99. The MIC was 2.00 in the main analysis. Secondary analyses revealed MICs of 0.50, 0.66, and 2.00 for small, medium, and large improvement, respectively. Conclusion The Nepali version of PSFS is a reliable, valid, and responsive measure. It can be used in clinical practice and research in Nepalese with musculoskeletal pain. J Orthop Sports Phys Ther, Epub 6 Apr 2018. doi:10.2519/jospt.2018.7925.