This study compared health-related quality of life (QOL) and psychological morbidity in a population-based sample of first generation immigrant and Anglo-Australian cancer survivors. Eligible participants, recruited via three State Cancer Registries, included those: with a new diagnosis of one of 12 most incident cancers (all stages) 1-6 years earlier; aged 18-80 at diagnosis; born in a Chinese, Arabic, or Greek speaking country and able to speak one of these languages. A random sample of English-speaking Anglo-Australian-born controls frequency matched for cancer diagnosis was recruited. 596 patients (277 of whom were immigrants) participated (a 26% response rate). In multiple linear regression models adjusted for age, sex, education, marital status, socio-economic status, time since diagnosis and type of cancer, immigrants had clinically significantly worse QOL (5.4-8.5 points on Functional Assessment of Cancer Therapy-General (FACT-G), P <0·0001), higher depression (P <0·0001) and higher incidence of clinical depression (P <0·01) than Anglo-Australians. Understanding the health system partially mediated this relationship for depression (P = 0·0004) and QOL (P = 0·001). Immigrant survivors of cancer have worse psychological and QOL outcomes than Anglo-Australians. Potential targets for intervention include assistance in navigating the health system, translated information and cultural competency training for health professionals. © 2013 Elsevier Ltd. All rights reserved.