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Background: Socioeconomic status (SES) is one of the main determinants of health-related quality of life (HRQoL), where people with lower SES experience more health problems, have a lower quality of life, and are exposed to have a greater number of health-related risk factors. Objectives: This study aimed to examine the relationships between HRQoL, SES, and several demographic factors among the residents of the city of Ilam (located at the West of Iran). Methods: This cross sectional study was conducted on 400 households from 3 districts of the city of Ilam in 2015. The participants were selected on the basis of the multistage sampling method. The second version of the 12-item Short-Form Health Survey (SF-12v2) questionnaire and the Wealth Index were used to measure HRQoL and SES, respectively. Results: The mean scores of the physical component summary (PCS) and the mental component summary (MCS) were 46.32 ± 9.69 and 42.12 ± 9.11, respectively. The findings indicated that PCS (P = 0.01) and MCS (P = 0.01) were significantly related to SES (wealth index). The demographic variables of age, gender, education level, marital status, job status, and home ownership (P < 0.05) were also significantly related to both PCS and MCS. Conclusions: HRQoL is directly related to SES, in that HRQoL is higher in families with higher SES. Similarly, HRQL is higher in younger people, men, and those with a university degree. A decrease in socio-economic inequalities and the gap between the rich and the poor can enhance the individuals’ health status and HRQoL within a community.