Diosgenin　(Di),　a　steroidal　sapogenin　derived　from　plants,　has　been　shown　to　exert　anticancer　effects　in　preclinical　studies.　Using　Di　as　a　starting　material,　various　Di　derivatives　were　designed　and　synthesized,　aiming　to　discover　new　steroid-based　antitumor　agents.　In　this　work,　we　synthesized　several　Di　derivatives　and　screened　FZU-0021-194-P2　(P2),　which　showed　more　potent　cytotoxic　activities　against　human　non-small-cell　lung　cancer　A549　and　PC9　cells.　Considering　that　Di　has　a　unique　sterol　structure　similarly　to　cholesterol,　P2　phytosomes　(P2Ps)　were　prepared　to　further　improve　the　water　solubility　of　P2.　The　P2Ps　exhibited　a　particle　size　of　53.6　+/-　0.3　nm　with　oval　shape　and　a　zeta　potential　of　-4.0　+/-　0.7　mV.　P2Ps　could　inhibit　the　proliferation　of　lung　cancer　cells　more　efficiently　than　Di　phytosomes　after　72　h　of　incubation　time　by　inducing　cell　cycle　arrest　and　apoptosis.　The　results　indicated　that　P2Ps　could　be　a　promising　anticancer　formulation　for　non-small-cell　lung　cancer.