Background: HIV-related stigma always is major obstacles to an effective HIV response worldwide. The effect of HIV-related stigma on HIV prevention and treatment is particularly serious in China. This study was to examine stigma attitude towards people living with HIV/AIDS (PLWHA) among general individuals in Heilongjiang Province, Northeast China and the factors associated with stigma attitude, including socio-demographic factors and HIV/AIDS Knowledge. Methods: A cross-sectional survey was carried out in Heilongjiang Province, China. A total of 4050 general individuals with age 15-69 years in four villages in rural areas and two communities in urban areas were drawn using stratified cluster sampling. Standardized questionnaire interviews were administered. Univariate and multivariate log-binomial regression were performed to assess factors affecting stigma attitude towards PLWHA. Results: The proportions of participants holding stigma attitude towards PLWHA were 49.6% among rural respondents and 37.0% among urban respondents (P < 0.001). Multivariate log binomial regression analysis among both rural participants (RR = 0.89, 95% CI: 0.87-0.91, P < 0.001) and urban participants (RR = 0.89, 95% CI: 0.87-0.91, P < 0.001) showed that greater knowledge of HIV transmission misconceptions was significantly associated with lower stigma attitude towards people living with HIV. And among urban participants, higher education level (high school vs. primary school or less: RR = 0.73, 95% CI: 0.62-0.87, P < 0.001; middle school vs. primary school or less: RR = 0.83, 95% CI: 0.71-0.97, P = 0.018) were also significantly associated with lower stigma attitude towards PLWHA. Conclusions: The level of stigma attitude towards PLWHA is higher in rural areas than in urban areas in Heilongjiang. Meanwhile, individuals who better were aware of HIV/AIDS transmission misconceptions may hold lower stigma attitude toward PLWHA whether among rural or urban residents.