Summary. Health-related quality of life (HRQoL) is an important aspect of the overall management of hepatitis B virus (HBV) infection. The major challenge is to find a valid and reliable disease-specific HRQoL instrument designed specifically for measuring health status in hepatitis B patient. Consequently, this study was undertaken to adapt culturally the Hepatitis Quality of Life Questionnaire (HQLQ) and assess its suitability for use in English-speaking hepatitis B virus-infected (HBV) patients in Singapore. Two patient focus groups were conducted to facilitate the cultural adaptation of the HQLQ. Reliability was assessed using Cronbach’s alpha coefficients and intraclass correlation coefficients. Item-to-scale correlation was assessed using Spearman’s rank correlations (ρ) between scale scores and their constituent items. Convergent and divergent construct validities were tested in three and two a priori hypotheses, respectively, and the correlations were assessed using Spearman’s rank correlation coefficients (ρ). The culturally adapted questionnaire was tested in 298 HBV patients. The test-retest reliability was supported with 10 of the 12 scales showing acceptable correlation coefficients (i.e. α > 0.7). Item-to-scale correlations were good with most items highly correlated with their hypothesized scales. Convergent and divergent construct validities were supported by the presence of hypothesized correlations between the HQLQ and the EQ-5D domains (eight of 10 sub-hypotheses for convergent construct validity and all hypotheses for divergent construct validity were fulfilled). In conclusion, our results showed that the culturally adapted HQLQ has good validity and reliability, making it a potentially useful outcome measure in the evaluation of HBV patients in Singapore.