Street people are prone for many infectious diseases including human immunodeficiency virus (HIV). This study assessed comprehensive knowledge, attitude and practice of street adults towards human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). A cross-sectional study was conducted on 325 street adults at two cities using a pretested questionnaire. Comprehensive knowledge on HIV/AIDS was assessed using five questions, attitude was measured using the Likert scale and practice by condom use and number of sex partners in the last one year. Descriptive statistics and bivariate/multiple logistic regressions were performed. The mean age of participants was 30.1± 9.0 standard deviation (SD) years. Majority (96.9%) had ever heard about HIV/AIDS. Main sources of information were radio (55.7%), neighbors (35.7%) and friends (33.2%). Only 31.4% had comprehensive knowledge, 23.7% favorable attitude and 27.7% used condom in their recent sexual intercourse. Almost a third (30.4%) had more than one sex partner in the last one year. Self-perceived risk of HIV infection was associated with knowledge, attitude and practice. The level of comprehensive knowledge, attitude and practice were low among street adults especially among those who cannot read and write. Prevention programs must equip street people with basic HIV/AIDS knowledge for behavioral change.