Illicit drug use is related to individual characteristics; however, social and family environments seem to be associated with this consumption. The aim of this study was to analyze the association of the relationships between parents or guardians and Brazilian adolescents that use illicit drugs. This is a cross-sectional study with data from the Brazilian National Survey of School Health (PeNSE, 2015), in which the target population was school children from the ninth grade (eighth year). A total of 102,072 students were included in the current research, being 52,782 females and 49,290 males. Illicit drug use was the outcome and family relationship factors were the exposure. For adjustments, factors as sociodemographic characteristics, mental health, as well as tobacco and alcohol use were established. Univariate and multivariate analysis stratified by sex was conducted through Poisson regression, with a robust variance estimator to calculate the prevalence ratio and the 95% confidence interval. The general prevalence of illicit drug use was 3.8%; 3.3% among females and 4.4% among males. The following factors increase the prevalence ratio for illicit drug use in adolescents: not living with their parents, not feeling supervised by parents, and skipping classes without parents' consent. Never feeling understood by parents and frequent physical aggressions by family members were also associated with illicit drug use. Family relationships collaborate to illicit drug use among Brazilian adolescents, considering their sociodemographic factors, alcohol and smoking habits and parents and friends' profiles.