The purpose of this study was the effect of entrepreneurial knowledge, independent attitude, creativity, entrepreneurial motivation on entrepreneurial interest in Muhammadiyah University Purwokerto students. This research uses quantitative research methods, probability sampling technique obtained through proportional stratified random sampling is a method of determining the sample randomly and proportionally by drawing lots or calculating proportionally. The sample of this research is 130 respondents. The research method used in this study is multiple linear regression. The results of the analysis show that simultaneously the variables of entrepreneurial knowledge, independent attitude, creativity and entrepreneurial motivation have effect on interest in entrepreneurship. Futhermore the partial test, the variables of independent attitude, creativity and entrepreneurial motivation have a positive and significant effect on interest in entrepreneurship, while the entrepreneurial knowledge variable does not partially affect interest in entrepreneurship.