A generalized eco-epidemiological system with prey refuge is proposed in this paper. The saturation incidence kinetics and a generalized functional response are used to describe the contact process and the predation process, respectively. Based on mathematical issue, the local and global stability properties, Hopf bifurcation, and permanence of the dynamical system are investigated. Based on the ecological aspects, the impact of prey refuge on the dynamical consequences of the eco-epidemiological system and the mechanism of prey refuge are discussed. The results reveal that the stabilizing and destabilizing effects occur under some certain conditions. Based on epidemiological issue, the controlling strategies of the infectious disease are proposed. The results show that the prey refuge can control the spread of disease by the relative level of prey refuge. This study has resolved some basic and interesting issues for an eco-epidemiological system with a generalized response function and the effect of prey refuge.