This research examines the knowledge and attitudes that Islamic Azad University students hold about substance abuse. A total of 3449 students from eighteen colleges who completed questionnaire, were randomly selected. The data analyze was done by T-test and ANOVA. The results revealed that students knew the factors of addiction and prevention methods of substance abuse (79.1% and 89.6%, respectively). The authors explored the differences between male and female college students’ attitudes toward factors of addiction (p<.01), treatment (p<.05) and prevention methods of substance abuse (p<.001). The results of ANOVA showed that there isn’t a significant difference between the knowledge of education groups students about factors of substance abuse and prevention programs.