This paper introduces the reform practice of the assignment design and evaluation system in the teaching process of the national excellent resource sharing course Microbiology in Huazhong Agricultural University for 2015–2017. The project is composed of three parts, including the “3211” tower design, binary evaluation system, the file record and the evaluation feedback mechanism. In each section, problems are designed according to the tower design: 3 basic questions + 2 divergent problems + 1 fixed question + 1 knowledge expansion problem. Two sets of system are adopted for correcting and evaluating homework. One is ABCD system which emphasizes knowledge and application and the assignment is graded by answering questions correctly. The other is M (model) system designed to encourage thinking and innovation, students are scored by their independent thinking spirit and scientific thinking ability. The corrected homework is sent back to the students in time. In the implementation of the project, we established files and recorded in detail each student’s job completion and gave them timely feedback. The information feedback includes the whole job briefing, homework questions review and model homework recommendation. We praise the exemplary students by scanning and uploading their model homework in the QQ group and encourage every student to make progress. After three years of teaching reform practice, it is proved that these measures can facilitate teaching and help teachers to clearly know how the students learn about the course, cultivate their independent thinking ability and scientific spirit of innovation, encourage their personal development and team collaboration, and achieved good results in practice.