Abstract: Purpose/Significance From the perspective of human resources management, in-depth research on the willingness of university researchers to innovate and entrepreneurship from the perspective of labor relations will not only better promote the scientific and technological talents of universities to actively integrate into the enterprise market, but also promote the cooperation of China’s industry, education and research, and enhance the national core competitiveness. Design/Methodology First, the scientific and technical personnel data of different types of colleges and universities in various regions of the country are collected through questionnaire survey methods, then the independent sample T test, single factor analysis method, and multi-level regression method are used for statistical analysis. Finally, the influence mechanism of welfare treatment, fair guarantee, development promotion on innovation and entrepreneurship willingness is obtained. Findings/Conclusions First, there is a significant difference in the willingness to innovate and start a business among scientific researchers of different genders and titles; second, the higher the level of welfare treatment, fair protection, and development promotion, the stronger the willingness to innovate and start a business. The impact on innovation and entrepreneurial intention is greater than fair guarantee, and fair guarantee has greater impact on innovation and entrepreneurial intention than development promotion. Third, welfare treatment, fair protection, and development promotion have positive two-way interaction effects on innovation and entrepreneurial intention. That is to say, the improvement of any one of the three variables will enhance the influence level of other variables on innovation and entrepreneurship willingness. In the future, college administrators and enterprise managers should provide scientific research personnel in colleges and universities with labor security guarantee conditions for innovation and entrepreneurship, so as to increase their willingness to innovate and start businesses.