Objective: To compare the prevalence of HIV infection and its risk factors among Chinese and Burmese drug users living in Dehong Prefecture, Yunnan Province. Methods: We obtained plasma specimens and gathered demographic data from 7 867 drug users with Chinese or Burmese nationality attending rehabilitation clinics in Dehong Prefecture from October 2014 to September 2015. Of these, 7 756 individuals who gave valid questionnaire responses, including 5 389 Chinese and 2 367 Burmese, were enrolled in the study after giving informed consent. We used the Chi-squared test to compare the demographic characteristics and HIV prevalence between the Chinese and Burmese drug users. Logistic regression was then used to identify risk factors for HIV infection. Results: The HIV infection rate of 7 756 subjects (aged (35.45 ± 10.91) years old) was 7.18%, in which Burmese with higher HIV infection rate (9.38%, 222/2 367) than Chinese (6.22%, 335/5 389) (χ2=24.21, P<0.001). In chinese drug users, OR (95%CI) of HIV infection of those aged 25-34 years old, 35-44 years old and ≥45 years old were 2.88 (1.46-5.69), 5.72 (2.87-11.40) and 3.48 (1.66-7.27),compared with those aged below 25 years;Compared with married participants, OR (95% CI) of those unmarried and divorced were 1.44 (1.08-1.93) and 1.56 (1.09-2.24); Jingpo drug users were 1.47 (1.07-2.04) times to get HIV infection,compared with Han ethnicity; OR (95%CI) of HIV infection for IDUs was 11.48 (9.73-16.01) compared with NIDUs.In Burmese drug users, OR (95% CI) of HIV infection for females was 0.50 (0.26-0.93) compared with men;Compared with those aged below 25 years,those aged 25-34,35-44 and ≥45 years had OR (95% CI) of 1.82 (1.18-2.77), 2.90 (1.82-4.62) and 2.31 (1.24-4.30), respectively; OR (95% CI) of Jingpo participants was 2.22 (1.44-3.41) compared with Han nationality; OR (95%CI) of HIV infection for IDUs was 10.61 (7.68-14.64) compared with NIDUs. Conclusion: The HIV infection rate of Burmese drug users was higher than that of Chinese drug users. Measures of HIV prevention and control should be mainly allocated in those 25 years above, non-married, Jingpo ethnicity and IDU in Chinese drug users, while in Burmese drug users,those females, 25 years above, Jingpo ethnicity and IDU should be higlighted in HIV prevention and control.