In the context of the Corona epidemic crisis, the mental health of individuals has been affected and has led to many issues, especially in the discussion of drug use. This study aimed to investigate the relationship between coronavirus anxiety and coping skills with substance use in Ardabil in 1400. The research method was case-control. So by referring to addiction treatment centers, 80 people using drugs were selected by the available sampling method and then 80 people as a control group were matched and compared with them in terms of some demographic variables. Subjects answered online forms of Weed’s Addiction Acknowledgement Scale (1992), Lee’s Coronavirus Anxiety Scale (2020), and Lazarus and Folkman’s (1984) Coping Skills Questionnaire, and the data were analyzed using t-test and logistic regression in SPSS-25 software. Substance users experienced a higher level of coronavirus anxiety compared to controls and used more emotion-oriented strategies to cope with stress. 79% of the variance of substance use tendency was explained by coping skills and coronavirus anxiety, of which emotion-oriented strategy (51%) had the largest share in prediction. Coronavirus anxiety and the use of ineffective stress management strategies, especially emotion-oriented strategies, play a role in drug addiction. Therefore, in the COVID-19 epidemic crisis, in addition to medical interventions for this disease, it is necessary to be aware of the psychological consequences of this crisis to prevent drug use.