Background: Illicit drug use is a major public health concern among university students. Objectives: The present study aimed to determine the prevalence of illicit drug use and the associated factors in a population of Iranian university students. Methods: This cross-sectional study was conducted in Bushehr, located in the Northwest of Iran in 2017. The participants were selected randomly and included 977 university students. Anonymous, structured questionnaires were completed by the students. The self-administered questionnaire consisted of data on illicit drug use, smoking habits, sexual behaviors, alcohol consumption, physical fights, religious beliefs, parental support, and illicit drug use by the family members and friends. Data analysis was performed using chi-square and logistic regression analysis. Results: The prevalence of illicit drug use during the lifetime, past year, past month, and daily/almost daily was estimated at 4%, 3.3%, 2.4%, and 0.9%, respectively. The lifetime prevalence of cannabis, amphetamine-type stimulants, opium, and heroin was 1.3%, 1.5%, 1.5%, and 0.1%, respectively. After adjustment for other factors, male gender (OR = 4.06), working along with education (OR = 2.33), smoking habits (OR = 4.00), physical fights (OR = 4.04), and illicit drug use by friends (OR = 2.71) were associated with illicit drug use. Conclusions: According to the results, the prevalence of illicit drug use was relatively low, albeit significant, among the students in Bushehr. Among the determined factors associated with this issue, illicit drug use was strongly correlated with drug use by friends. Our findings could be used for the planning and evaluation of interventions based on the related risk factors.