Entrepreneurial skills are instilled to overcome future labor market challenges, in line with government directives. This aims to change the mindset of the younger generation from job seekers to job creators. Application book based worksheet Biotechnology on eye studying Bioentrepreneur aim For increase interest And creativity student entrepreneurship . This development research uses the ADDIE development model which consists of five stages: (1) Analysis, (2) Design, (3) Development, (4) Implementation, and (5) Evaluation. Validation from experts, such as: validation of subject matter experts, validation of learning media experts, and validation of learning design experts. Apart from that, feasibility and practicality questionnaires were also conducted by teaching lecturers, small groups and students using Biotechnology-based worksheet books. Results evaluation creativity with N-Gain value of 80% with category interpretation effective . Whereas mark effectiveness For interest businessman with N-Gain value 54%, with interpretation not enough effective . Reviewed from questionnaire evaluation student with LKM, determined mark appropriateness amounted to 88.7 % , and the practicality value was 85%..