Health literacy and self efficacy are factors in increasing drug abuse prevention behavior. Therefore, high health literacy and self efficacy are needed in order to increase good behavior in preventing drug abuse. This study aims to determine the relationship between health literacy and self efficacy with drug abuse prevention behavior in youth Posyandu in the working area of the Kampung Bugis Community Health Center, Tanjungpinang City. The research is a quantitative study with a cross sectional design. The population is 60 respondents, and the sampling technique uses total sampling. Data collection using a questionnaire. Data analysis used the Spearman tho correlation test. The univariate result showed the proportion of high health literacy (68, 3%), high self efficacy (75%), and good drug abuse prevention behavior (88,4%). The results of the bivariate analysis of health literacy obtained pvalues = 0,009 (p <0, 05) self effect obtained p value = 0,015 (p <0, 05) with drug abuse prevention. It was concluded that there is a relationship health literacy and selfe efficacy with drug abuse prevention behavior in youth posyandu in the working area of the Bugis Village Health Center.