To examine the relationship of family functioning on health-related quality of life (HRQoL) among methadone maintenance patients using the Bayesian approach. A cross-sectional study was conducted on 182 patients at Go Vap Methadone Clinic, Ho Chi Minh City, Vietnam. Family functioning and HRQoL were measured by the APGAR scale and World Health Organization Quality of Life short-form instrument (WHOQoL-BREF), respectively. Directed Acyclic Graphs were used to present the conceptual framework and to identify a set of confounders of the relationship between family functioning and HRQoL. Bayesian multivariable linear regressions were fitted with four different priors to determine the effect size of the relationship of interest. The mean score of APGAR was 6.0 (SD = 3.3), and the mean scores of HRQoL were from 47.1 (SD = 17.6) in the social relationships dimension to 69.0 (SD = 10.3) in the environment dimension. Patients with a higher score of family functioning were likely to have a higher score of HRQoL, with coefficients and 95% highest density interval (HDI) greater than 0 in all priors. Family functioning had the most substantial impact on the psychological health dimension, with 99.9% to 100% and 44.6% to 83.7% of posterior distribution greater than 1 and 2, in different priors, respectively. Family functioning is intimately associated with HRQoL. Treatment plans for patients undergoing methadone maintenance treatment should aim to involve the families appropriately and effectively to maximize the benefits for patients and improve their overall well-being.