In middle adolescence, young people being aware of self have more self-efficient in developmental issues due to their self-regulation. In this sense, thriving based on the self-regulation approach is thought to be a mediator for adolescents to experience self-efficacy and mindfulness. Thus, this study was aimed to investigate thriving as a mediator on the relationship between mindfulness and self-efficacy among high school students. A total of 309 high school students (245 females, 64 males), with the average age 16.97 (SD = 0.69), attending Uskudar Municipality Youth Academy in Istanbul between 2018-2019 for assistance towards their university exams participated in this study. The 44.1% of participants (n = 136) were in Grade 11, and 55.9% (n = 173) were in Grade 12. Mindfulness Attention Awareness Scale, Thriving at School Scale, and General Self Efficacy Scale were applied on participants to collect data. Pearson correlation coefficients were calculated to detect the relationship between variables, and the mediating role of thriving on the relationship between mindfulness and self-efficacy was tested using a simple mediation model. Results showed that variables were significantly correlated to each other, and thriving increases with increased mindfulness, while self-efficacy increases with increased thriving. The mediation model in its entirety proved statistically significant, accounting for 23% of the total variance. The findings have been discussed in line with relevant literature on the issue and recommendations on their possible application have been given.