The　study　dealed　with　quantitative　structure-activity　relationship(QSAR)　to　explore　the　important　features　of　diketo　acid(DKA)　derivatives　for　exerting　potent　HIV-1　integrase　inhibitors　activity.　A　three-step　screening　method　was　proposed　to　choose　descriptors.　Then,　additional　descriptors　were　used　in　the　CoMFA　and　CoMSIA.　Lastly,　a　modified　CoMSIA　m7　model,　constructed　by　adding　C-sp(2)_03_F　descriptor,　showed　better　predictive　ability.　Validation　parameters(Q(2)　and　R-2)　for　the　models　were　0.722　and　0.925,　respectively.　In　addition,　external　validation　for　the　models　using　a　test　group　revealed　Rpred2　=0.892.　Contour　maps　analysis　defined　favored　and　disfavored　regions　of　the　compounds,　and　two　new　compounds　with　the　descriptor　structure　were　designed　with　better　activities　than　Raltegravir(RAL),　well　drug-likeness　and　low　toxicity.　The　research　provides　a　base　for　further　DKA　development.