Background and aims: One of the most important problems of public health is illicit drug use. The aim of this study was to assess the status of illicit drug use and associated factors among hookah smokers in Khalil Abad city in 2015. Methods: The cross-sectional study was conducted in Khalil Abad city (northeast of Iran) in 2015. A sample of 161 hookah users was selected using 2-stage sampling. Structured questionnaires were distributed among the subjects and participants were included in the study after completing informed consent form. To analyze the data, we used chi-square, t test and logistic regression model. Results:The prevalence of illicit drug use was 36%. The result of final logistic regression model, with inclusion of confounders, showed that job status (odds ratio [OR] = 4.13), smoking in the last year (OR = 3.84) and prescription opioid drug use (OR = 3.77), were associated with illicit drug use. Conclusion: Our results showed high prevalence of illicit drug use, which was strongly associated with unemployment and other substances use. The results of this study can be used for planning for epidemiological studies in national scale in order to implement and evaluating interventions by considering the risk factors of hookah smoking in this type of individuals.