The aim of this study is to evaluate a core-shell nanofiber as a useful matrix for tuning Rosuvastatin (RSV) release and osteogenic differentiation in vitro. Polyvinyl alcohol (PVA) and silk fibroin were used as the shell and the core, respectively. To obtain a linear and beadless core-shell structure and an optimal release profile, the shell/core flow rate ratio was varied (0, 0.4, 0.6, 0.8, and 1). Formation of continuous nanofibers with an obvious core/sheath structure was proved using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Differential scanning calorimetry indicated the presence of two distinct phase structures in the nanofibers. Also, RSV molecules were dispersed in an amorphous state in the nanofibers. The in vitro release profile of the core-shell structure exhibited a biphasic release profile and the amount of released RSV was controlled by adjusting the shell flow rate. Human adipose-derived stem cells cultured on the RSV loaded nanofibers were found to improve cell proliferation and assist osteogenic differentiation as revealed by Alizarin red staining and real-time RT-PCR.