BACKGROUND: EQ-5D-3L has been used in the National Health Services Survey of China since 2008 to monitor population health. The five-level version of EQ-5D was developed, but there lacks evidence to support the use of five-level version of EQ-5D in China. This study was conducted to compare the measurement properties of both the EQ-5D-3L and EQ-5D-5L in quantifying health-related quality of life (HRQoL) burden for 4 different health conditions in China. METHODS: Participants from China were recruited to complete the 3L and 5L questionnaire via Internet. Quota was set to recruit five groups of individuals, with one group of individuals without any health condition and one group of generalized anxiety disorder (GAD), HIV/AIDS, chronic Hepatitis B (CHB), or depression, respectively. The 3L and 5L were compared in terms of response distributions, percentages of reporting 'no problems', index value distributions, known-group validity and their relative efficiency. RESULTS: In total, 500 individuals completed the online survey, including 140 healthy individuals, 122 individuals with hepatitis B, 107 with depression, 90 individuals with GAD and 101 with HIV/AIDS. 5L also had smoother and less clustered index value distributions. Healthy group showed different response distributions to the four condition groups. The percentage of reporting 'no problems' decreased significantly in the 5L in all domains (P < 0.01), especially in the pain/discomfort dimension (relative difference: 43.10%). Relative efficiency suggested that 5L had a higher absolute discriminatory power than the 3L version between healthy participant and the other 4 condition groups, especially for the HIV/AIDS group when the 3L results was not significant. CONCLUSIONS: The 5L version may be preferable to the 3L, as it demonstrated superior performance with respect to higher sensitivity to mild health problems, better relative efficiency and responses and index value distributions.