Objective  To examine the cognition on and the demand for knowledge about human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) among senior high school students in Jiangsu province and to analyze regional difference in the cognition and demand and its influencing factors for providing evidences subsequent interventions.

  Methods  We conducted a cross-sectional survey with a self-designed and self-administered questionnaire among 3 762 senior students recruited in 6 high schools in the southern, central, and northern areas of Jiangsu province with random cluster sampling between June and August 2016. χ² test was used to assess the regional differences in AIDS knowledge and logistic regression analysis was employed to explore relevant influencing factors.

  Results  Among the 3 590 students with valid responses, the overall awareness rate of AIDS knowledge was 50.5%, with a significantly higher rate among the students in the southern area than that among the students in central and northern areas (63.5% vs. 57.8% and 31.8%, both P < 0.05) and a statistically higher rate among the boy students than among the girl students (52.9 % vs. 48.6%, P < 0.05). The results of logistic regression analysis demonstrated that the students in southern and central areas (odds ratio OR_southern = 3.593, 95% confidence interval 95% CI: 3.026 – 4.266; OR_central = 2.871, 95% CI: 2.431 – 3.391) and the students living with parents (OR = 1.332, 95% CI: 1.066 – 1.666) were more likely to have a higher awareness rate compared to the students in the northern area and those not living with parents. The major sources of HIV/AIDS-related knowledge reported by the students were internet (reported by 62.8% of the students), classmates and friends (50.0%), books (48.1%), and teachers (47.8%). Almost all the students (> 90%) considered that HIV/AIDS-related education would be helpful for their development and expressed the willingness to acquire more relevant knowledge.

  Conclusion  There are significant regional differences in the level of HIV/AIDS-related knowledge among senior high school students in Jiangsu province and the students in northern Jiangsu have a lower level of knowledge about HIV/AIDS. The results suggest that health education should be improved among the students in the northern region in addition to overall promotion of health education on HIV/AIDS among the students in the province.