The development of nations involves the generation of innovations. Thus, university-enterprise (U-E) interaction is an institutional arrangement that belongs to the National Innovation System, which enables the interaction between scientific and technological production. This interaction is essential and strategic in generating innovative processes. The objective of this study is to analyze the difficulties and facilitating mechanisms present in the process of U-E interaction in the Public Universities of Santa Catarina. To this end, a theoretical and empirical, descriptive, ex-post facto, literature, and multi-purpose study was conducted, using a qualitative approach. Interviews were conducted with key actors in this process in universities. The discussion of the study was focused on three categories of analysis: the context of universities, the difficulties, and mechanisms that facilitate U-E interaction. Among the main difficulties found in the process of interaction are the legislations to which the public institutions are linked, the absence of a clear domestic policy and consensus in institutions, incompatible terms of contract, and differentiated goals. The main facilitating mechanisms identified were: resolutions in the area of research activity, the creation of an innovation committee, coordinator and committee, the launch and reformulation of technological innovation centers, government incentives to carry out cooperative research, approach and creation of incubators and technology parks, and the inclusion of objectives related to interaction and technological development within the institutional development plan.