OBJECTIVES: To evaluate association between patients’ knowledge of Hepatitis-B and Health Related Quality of Life (HRQoL).  METHODS: A cross sectional, descriptive study was undertaken with 390 Hepatitis-B patients attending two public hospitals of Quetta city, Pakistan. Knowledge towards hepatitis-B was assessed by using a pre validated questionnaire. European Quality of Life scale (EQ-5D) was used for the assessment of HRQoL. Descriptive analysis was used for elaborating patients’ demographic characteristics. HRQoL was scored using values derived from the UK general population survey. Spearman’s rho correlation was used to identify the association between variables. All analyses were performed using SPSS 16.0 RESULTS: Two hundred and thirty two (59.5%) were males with mean age of 36.21±9.2 years. 103 (26%) had primary level of education with 109 (27.9%) were working in private sector. Eighty four (21%) had monthly income of in between 10001-15000 Pakistan rupees with 272 (69.7%) having urban residency. HRQoL was measured as poor in our study patients (0.46±0.25). Mean knowledge score was categorized as poor (8.52 ± 2.746). Correlation coefficient between HRQoL and knowledge was -0.102, indicating a week negative association between the study variables. CONCLUSIONS: Results of the present study show that patients’ knowledge of hepatitis B is weakly correlated with HRQoL. Having better and correct disease related knowledge could be useful in clinical practice, especially in early stages of hepatitis B, where improving HRQoL could still be possible.