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This study aimed to develop critical thinking skills through Culturally Responsive Teaching (CRT) approach and ethnochemistry of Tegal culture. The teaching approach is focusing on exploring the culture and local wisdom in Tegal Culture especially in Acid-Base such as Jamasan Tradition, Nginang, and Moci from chemistry perspectives integrated into CRT. The study employed the teaching model which consists of five phases of self-identification, cultural understanding, collaboration, critical reflections, and transformative construction. The study involved 35 students of year 11 in secondary school in Balapulang Tegal. The qualitative methodology approach has been employed with observation, interviews, critical thinking test, and reflective journals as data collection. The results showed that the integration of ethnochemistry in CRT approach has engaged students in developing their critical thinking skills in developing a conclusion, making the connection, conceptual understanding, and interpretation with the critical thinking skills test shows 40% students have reached level 3 (Satisfactory). In addition to the students engaged in the cultural identity empowerment, meaningful chemistry learning experiences, and team working. The students have been challenged in developing their critical thinking skills.