Introduction: Human immunodeficiency virus infection / acquired immune deficiency syndrome (HIV/AIDS) and tuberculosis are the most important communicable diseases in vulnerable populations. Objectives: The aim of this study was to determine the prevalence of HIV/AIDS and tuberculosis among homeless individuals in Shiraz, Iran. Patients and Methods: This is a cross-sectional study which was carried out on 589 homeless men and women in Shiraz city. The data collection tool was a structurally standard questionnaire. After filling questionnaire, ELISA test was taken each person. If the results of the ELISA test were positive, then, a complementary Western blot test was conducted for HIV. Accordingly a PPD was conducted for individuals suspected to tuberculosis. Data were analyzed by ANOVA and student t test. Results: HIV prevalence in this population was 7.6%. Around 8.88% of HIV positive cases were men. Around 2.37% of the cases had an experience of drug injection. The difference between cases with positive test of HIV in drug users and those who did not use drugs was statically significant (P < 0.05). Around 34.7% of men had experienced homosexual relations. Conclusion: In this study, prevalence of HIV in participants was 7.6%, therefore much more attention needs to be paid to the health of homeless people.