In this study, biodegradable and biocompatible polycaprolactone (PCL) nanoporous membranes have been successfully prepared via the combination of thermally and nonsolvent induced phase separation techniques. The polymer solution with a specific composition was cast on a suitable plate. Then, the cast film of the solution was immersed into a lower temperature coagulation bath, i.e., both thermally and nonsolvent induced phase separations took place simultaneously. In the membrane preparation, the thermally induced phase separation could enhance porosity or avoid the formation of a dense top-layer. On the other hand, the nonsolvent induced phase separation could play a role on the formation and the dimension/size of nanoscale pores. Our results showed that the pore size reduced and the porosity increased as the coagulation bath temperature decreased. Also, the release rate of the model drug compound, lysozyme, into an aqueous solution was higher as a lower coagulation bath temperature was used. As a result, the drug release rate can be well controlled via adjusting the parameters for the membrane preparation, including coagulation bath temperature and casting solution composition. In addition, the nanoporous membrane provides a barrier for preventing the passage of cytotoxic cells, macrophages, antibodies and other immune substances.