In　addition　to　its　well-known　abortifacient　effect,　mifepristone　(MIF)　has　been　used　as　an　anticancer　drug　for　various　cancers　in　many　studies　with　an　in-depth　understanding　of　the　mechanism　of　action.　However,　application　of　MIF　is　limited　by　its　poor　water　solubility　and　low　oral　bioavailability.　In　this　work,　we　developed　a　drug　delivery　system　based　on　chitosan　nanoparticles　(CNs)　to　improve　its　bioavailability　and　anticancer　activity.　The　MIF-loaded　chitosan　nanoparticles　(MCNs)　were　prepared　by　convenient　ionic　gelation　techniques　between　chitosan　(Cs)　and　tripolyphosphate　(TPP).　The　preparation　conditions,　including　Cs　concentration,　TPP　concentration,　Cs/MIF　mass　ratio,　and　pH　value　of　the　TPP　solution,　were　optimized　to　gain　better　encapsulation　efficiency　(EE)　and　drug　loading　capacity　(DL).　MCNs　prepared　with　the　optimum　conditions　resulted　in　spherical　particles　with　an　average　size　of　200　nm.　FTIR　and　XRD　spectra　verified　that　MIF　was　successfully　encapsulated　in　CNs.　The　EE　and　DL　of　MCNs　determined　by　HPLC　were　86.6%　and　43.3%,　respectively.　The　in　vitro　release　kinetics　demonstrated　that　MIF　was　released　from　CNs　in　a　sustained-release　manner.　Compared　with　free　MIF,　MCNs　demonstrated　increased　anticancer　activity　in　several　cancer　cell　lines.　Pharmacokinetic　studies　in　male　rats　that　were　orally　administered　MCNs　showed　a　3.2-fold　increase　in　the　area　under　the　curve　from　0　to　24　h　compared　with　free　MIF.　These　results　demonstrated　that　MCNs　could　be　developed　as　a　potential　delivery　system　for　MIF　to　improve　its　anticancer　activity　and　bioavailability.