Abstract: On the basis of the overall analysis of work safety responsibility matrix, a new method for carrying out the main body responsibility of enterprise safety work is further proposed. Centering on work safety responsibility management of enterprises, the paper decomposes the task of work safety management drastically, defines the role of all enterprise safety departments and personnel clearly, and establishes a general type of work safety management responsibility matrix of the small and medium-sized enterprises according to the principle of one to one about safety work tasks and roles. The work safety management responsibility matrix can manifest clearly the responsibility of safety work, which is beneficial to improving the main body responsibility of enterprise safety work. The establishment of the enterprise work safety management responsibility matrix provides certain reference and guidance for the implementation of enterprise work safety responsibility as the main production.