BackgroundSubstance use in adolescents is a global public health concern that continues to draw attention from academics, policy experts, and government officials. In Morocco, few studies have investigated the influencing factors of substance use in adolescents. Here, we aimed to fill this gap and to better understand factors that protect or influence substance use in adolescents.MethodsWe conducted a qualitative study using focus group discussions. The semi-structured interview guides were based on the socio-ecological model as a theoretical framework to explore perceptions of students, parents, and teachers regarding substance use risks and protective factors in adolescents. Data from each group were audio-recorded, transcribed, and analyzed using thematic analysis.ResultsFrom May to July 2016, 17 focus group discussions were conducted at two middle schools in Taza city, Morocco, which included 8 groups of 7 adolescents (28 boys and 28 girls) aged 14 to 16 years, 5 groups of parents (5 females and 21 males), and 4 groups of teachers (13 males and 5 females). Thematic analysis resulted in six common themes that represented the most salient perceived risk and protective factors regarding substance use among adolescents: perceived benefits of substance use, awareness and beliefs, family influence, peer influence, easy accessibility of substances, and social norms.ConclusionsOur results demonstrate that multilevel prevention programs in adolescents should address influencing factors from the individual to the societal level, including social norms and the government’s policy toward substance use. Health education programs included as part of the school curriculum can contribute to promoting awareness and reducing risky behaviors of Moroccan adolescents.