This study explored the effects of cognitive-behavioral program (CBP) using a wait-list control group in 16 Chinese heterosexual HIV-infected men. Participants in the treatment condition underwent a 7-week group based CBP, which addressed various HIV-related issues. Relevant cognitive and behavioral strategies were taught as well. The aim of treatment was to improve the quality of life and to reduce psychological distress in a sample of heterosexual symptomatic HIV-infected men. Prior to intervention, baseline measures showed that our sample had a lower quality of life in comparison with the local general population. They also experienced a significant level of psychological distress. Following intervention, men in the CBP group demonstrated significant improvement in the mental health dimension of quality of life and a significant reduction in depressed mood. These preliminary findings suggested that short-term cognitive-behavioral therapy can be effective in improving the quality of life and mood of Chinese heterosexual HIV-infected men.