The "Merdeka Belajar" curriculum will bring changes to the learning system in schools. This curriculum strives for a free learning process according to the interests and character of students. Students and teachers are free to innovate to improve the quality of learning according to the era of the industrial revolution 4.0, which is engaged in digital and technology. Biotechnology material is a development of technology-based natural science. This study aims to describe the “Merdeka Belajar” curriculum and its challenges in the industrial revolution 4.0 on Biotechnology material. This research method used library research or literature review. Research based on literature reviews obtained from books, journals, and several other sources attempts to analyze all the data gathered from various sources by inputting keywords using database. The challenges of education in the era of the industrial revolution 4.0 are related to efforts to prepare graduates with various skills and the need to prepare educator resources, Articularly instructors with instructive competence, competence in inquire about, competence for mechanical commercialization, competence in globalization, and competence in future methodologies. Learning activities that can be done to support biochemistry learning in the era of the industrial revolution 4.0 and the “Merdeka Belajar” curriculum are Artificial Intelligence (AI) Biotechnology, Biotechnology Metaverse, Implementation of Project-Based Biotechnology Learning, and Visit Biotechnology Factory.

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