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Background: To investigate the relationship between obesity and health-related quality of life (HRQL) in a randomly selected Chinese sample. Methods: A total of 3600 residents aged 18–80 years were sampled in five cities of China using a randomized stratified multiple-stage sampling method to receive the interview, with a self-completed questionnaire to collect demographic information, and the Mandarin version of Short Form 36 Health Survey questionnaire (SF-36) to assess HRQL, followed by height and weight measurements for calculating body mass index (BMI). Cross-sectional association between BMI and HRQL was analysed. Results: Among the 3207 participants (mean age 42 years) suitable for analysis, BMI differed by age and gender. Based on the international or the Asian BMI categories, in women, meaningful impairments were seen between obese and normal weight participants in four physical health scales, and only one scale of the four mental health scales—vitality scale was affected by obesity; in men, impairments by obesity were not found in all of the eight SF-36 scales, and better HRQL in two mental health scales were observed in obese participants compared to normal weight ones; after adjusting related variables, several physical but not mental health scales were found impaired by obesity. Conclusion: Obesity impaired physical but not mental health, and the impairments varied between genders. Public health agencies and government should emphasize the impairments of obesity on physical health. [ABSTRACT FROM AUTHOR]