The empirical study reported here aims to improve the effectiveness of knowledge-based talent management in science and technology enterprises and promote the stable development of enterprises. First, the impact of entrepreneurs’ psychological cognition and personal characteristics on entrepreneurial activities is analyzed based on entrepreneurial psychology. Then, the theory of key competence is introduced to study the management mode of knowledge-based talents. The advantages of talents in enterprises are sorted out through constructing the key competency model to manage talents efficiently. The technology-based enterprise M is taken as an example for analysis by the key competence model to obtain 18 key capability indexes. Through the principal component analysis of 255 employees’ survey results, finally, four factors are extracted (business execution ability, team cooperation ability, strategic thinking ability, and management decision-making ability), which can reflect 68.92% of the total key competence. The average values of “business execution ability” and “team cooperation ability” in the first-level dimension of key competence index are 4.14 and 4.24, respectively, which can be regarded as the essential key competence. The investigation results of the academic qualifications of staff of M indicate that 6% of employees have a doctorate, 38% have a master’s degree, 37% have a Bachelor’s degree, and 19% have a junior college degree or below. Moreover, knowledge-based employees are basically satisfied with the organization and management of the company, but they are dissatisfied with the training mechanism and promotion mechanism. Therefore, enterprises should pay attention to the psychological needs of knowledge workers and the innovation of talent management. The research results are of significant value for science and technology enterprises to absorb and retain knowledge-based talents and promote the common development of enterprises and employees.