The folic acid (FA) and doxorubicin (DOX) have been doped into the g-C3 N4 /MoS2 incorporated-chitosan/ethyl cellulose (EC) core-shell nanofibers for targeted delivery of FA and DOX against HeLa and MCF-7 cell lines. The g-C3 N4 /MoS2 nanosheets and core-shell nanofibers were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and UV-Vis tests. The drug loading factor, the degradation rate, and the DOX and FA release behavior from core-shell nanofibers have been investigated. The pharmacokinetic results revealed the linear release with non-Fickian diffusion of the both anticancer drugs from nanofibers during 7 days. The DAPI staining and MTT assays of the nanofibers immersed in MCF-7 and HeLa cell lines were studied to determine the potential of DOX and FA doped-core-shell nanofibrous matrix for MCF-7 and HeLa cells death in vitro. The maximum MCF-7 and HeLa cells death percentages were found to be 89 and 85%, respectively, using EC/chitosan/g-C3 N4 /MoS2 /DOX/FA core-shell nanofibers after 7 days. The high activity of g-C3 N4 /MoS2 /DOX/FA loaded-core-shell nanofibers for studied cancer cells killing was achieved.