The creative problem solving (CPS) based on genetic mutation module provides students with an opportunity to identify problems, design a problem-solving plan, choose the right path, and effectively evaluate the solution. This research aims to examine the effectiveness of CPS-based genetic mutation module to improve problem-solving skills in undergraduate students of biological education. Furthermore, the CPS module was developed on the basis of research and development (R&D) according to the Borg and Gall method and presented as a mutation module for genetic material. A group pre-test and post-test design was applied by undergraduate students of biological education at the university of Sebelas Maret in Surakarta using random sampling techniques. A total of 17 students from 5 th semester were accepted as participants and treated for pre-test and post-test. The instruments used for the collection of data was an essay test design based on Polya's indicators of problem-solving skills. In addition, this module was considered as an advantage in using large database storage technologies such as NCBI and ExPASy in order to solve the problem-solving process. The application of the module has been shown to be effective in improving students' problem solving skills from a very low to a moderately high level.