Liposomes and nanofibers have been introduced as effective drug delivery systems of anticancer drugs. The performance of chitosan (core)/poly(ε-caprolactone) (PCL)/paclitaxel simple nanofibers, chitosan/paclitaxel (core)/PCL/chitosan (shell) nanofibers and paclitaxel-loaded liposome-incorporated chitosan (core)/PCL-chitosan (shell) nanofibers was investigated for the controlled release of paclitaxel and the treatment of breast cancer. The synthesized formulations were characterized using polydispersity index, dynamic light scattering, zeta potential, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared analysis. The sustained release of paclitaxel from liposome-loaded nanofibers was achieved within 30 days. The release data was best described using Korsmeyer-Peppas pharmacokinetic model. The cell viabilities of synthesized nanofibrous samples were higher than 98 % ± 1 % toward L929 normal cells after 168 h. The maximum cytotoxicity against MCF-7 breast cancer cells was 85 % ± 2.5 % using liposome-loaded core-shell nanofibers. The in vivo results indicated the reduction of tumor weight from 1.35 ± 0.15 g to 0.65 ± 0.05 g using liposome-loaded core-shell nanofibers and its increasing from 1.35 ± 0.15 g to 3.2 ± 0.2 g using pure core-shell nanofibers. The three-stage drug release behavior of paclitaxel-loaded liposome-incorporated core-shell nanofibers and the high in vivo tumor efficiency suggested the development of these formulations for cancer treatment in the future.