Substance use among university students is a common problem in the world. However, there are insufficient data on its prevalence among health school students. Similarly, there are very few studies about the use of substances by health students in Turkey. These studies have been mostly limited to the use of alcohol and tobacco. To the best of our knowledge, no previous studies have examined the substance use among students studying at health-related departments. This study investigated the pattern of substance abuse and its relationship with social support, self-efficacy, emotional quality of life, and sociodemographic factors in health profession students. Data of the cross-sectional and correlational study were collected via WhatsApp. Participants completed a student information form, the Substance Abuse Proclivity Scale, the Drug Abuse Screening Test, the Multidimensional Scale of Perceived Social Support, the SF-36 Emotional Quality of Life Index, and the Self-Efficacy for Protecting from Substance Abuse Scale. Of the participants, 63.6% (n = 823) had a high proclivity for substance abuse. Students most frequently used cigarettes and cannabis, one of the narcotic drugs. Substance abuse and proclivity increased as the emotional quality of life, social support, and self-efficacy decreased ( p < .05). Substance abuse proclivity and drug use were higher in men, immigrants, smokers and alcohol users, those with a trauma history, and those separated from their family ( p < .05). Health education reduces substance use ( p < .05). It is required to make attempts to prevent and eliminate substance abuse in health profession students.