Performing a training program for reducing nurses’ discrimination towards AIDS clients, and then evaluating the effect of the training model and analyzing the influencing factors of the training effect to form a long-run training model. 150 clinical nurses were selected to attend the program to reduce nurses’ discrimination towards AIDS clients. The program included 3 steps: knowledge education, psychological intervention, and behavior correcting. Before the program, we conducted pre-research to learn the current situation, including existing discrimination and training needs. Selected nurses were asked to complete questionnaires before and 6 months after training, and the trainees were from several hospitals in Haikou. The research period was from March to September 2020. The scores for AIDS-related knowledge, discrimination attitudes, and nursing standard behavior before training were (49.69 ± 3.80), (47.01 ± 3.70), and (35.98 ± 3.01), respectively, and the scores from 6 months after training were (59.01 ± 3.88), (52.19 ± 4.98), and (38.12 ± 2.98), respectively. Correlation analysis revealed that the scores for the nurses’ AIDS-related knowledge and behavior were positively correlated ( R = 0.31, P < .05); however, there was no correlation found between attitude and behavior ( P > .05); no significant differences were observed in the 3 scores among nurses in different departments and nurses with different working durations. There was a significant difference detected among nurses in their experience caring for AIDS clients ( F = 3.80, P < .05). The nurses with higher education levels also showed a significant difference compared to those with low education levels on their knowledge and behavior scores ([ F = 3.49, P < .05] and [ F = 4.68, P < .05], respectively). AIDS-related knowledge training and psychological intervention can effectively reduce the discriminatory attitudes of nurses towards AIDS clients.