To date, no studies have examined loneliness in Chinese patients with substance use disorders. This study determined the prevalence and socio-demographic and clinical correlates of loneliness and its impact on quality of life (QOL) in Chinese heroin-dependent patients (HDPs) receiving methadone maintenance treatment (MMT). A total of 603 HDPs were consecutively recruited from three city-owned MMT clinics in Wuhan, China, and administered with a standardized questionnaire to collect socio-demographic and clinical data. Loneliness and QOL were assessed with a single-item self-report question and World Health Organization QOL Scale Brief Version, respectively. As high as 55.9% Chinese HDPs of MMT clinics endorsed loneliness. Multiple logistic regression found that non-married status, unemployment, religious beliefs, a history of injecting heroin, poor interpersonal relationship, and more depressive symptoms were significant contributors to loneliness. Lonely HDPs had significantly poorer physical and psychological QOL than not lonely HDPs. After controlling for the potential confounding effects of socio-demographic and clinical factors with analysis of covariance, these group-differences in physical (F = 127.169, P < 0.001) and psychological (F = 85.004, P < 0.001) QOL remained statistically significant. Loneliness is prevalent in HDPs receiving MMT and independently associated with poor QOL. To address this serious issue, psychosocial services, including the identification of psychosocial problems, expanded social supports that focus on promoting mental wellbeing, and, when necessary, psychiatric assessment and treatment, should be routinely provided in Chinese MMT settings.