Ethnicity is one of the critical factors in achieving learning outcomes. A specific learning model is needed to overcome the learning process with multi-ethnic students. Quasi-experimental research was carried out with four majoring ethnicities, i.e., Javanese, Banjar, Kutai and Buginese, in senior high school with class XI majoring in natural science in Samarinda. This study aimed to determine the effect of applying PBL supported by Think-Pair-Share learning models in empowering the understanding of concepts about cells and tissues of the four ethnicities' students. The experimental design used a nonequivalent pretest-posttest control group. The instrument was a questionnaire for the survey and questions for the pretest-posttest. The data were analysed by Analysis of Co-Variance followed by the LSD test. The results showed that the application of PBL supported by Think-Pair-Share significantly affected (p < 0.05) the concepts understanding of multi-ethnic students about cells and tissues.