Background: Sexual and gender-minority (SGM) adolescents are more likely than their heterosexual and cisgender peers to smoke cigarettes. Family rejection has been associated with adverse health outcomes; however, few studies have examined whether SGM-specific family rejection is associated with cigarette smoking among SGM adolescents. Methods: A non-probability sample of 11,005 SGM adolescents (M = 15.58, SD = 1.27) completed an online cross-sectional survey. Bivariate and multivariable analyses were conducted to examine associations between SGM-specific family rejection, sociodemographic variables, and smoking. Results: Approximately 7% of the sample currently smoked cigarettes. Pansexual, asexual, trans boys, and non-binary assigned female at birth adolescents had the highest SGM-family rejection scores. In multivariable regression analyses, SGM-specific family rejection was independently associated with smoking after adjusting for covariates (AOR=1.15, 95% CI: 1.04, 1.28). Family support (AOR=0.80, 95% CI: 0.73, 0.88) and experiencing violence (AOR=1.64, 95% CI: 1.49, 1.82) were also associated with smoking in multivariable models. Adolescents who identified as bisexual vs gay/lesbian (AOR=1.50, 95% CI: 1.21, 1.85) and trans boys (AOR=2.05, 95% CI: 1.13, 3.71) vs cisgender girls had an increased odds of smoking. Those who disclosed their sexual orientation identity to most (AOR=1.95, 95%CI 1.45, 2.63) and all (AOR = 1.60, 95% CI: 1.21, 2.11) of their family/parents had increased odds of smoking.