OBJECTIVE To prepare curcumin /berberine co -loaded self -microemulsion drug delivery system （CUR/BER- SMEDDS）and evaluate its physicochemical properties and in vitro anti-tumor effects . METHODS Using CUR and BER as model drug，based on the screening of the type of oil phase ，emulsifier，co emulsifier and their mass ratio ，the formulation of CUR/BER - SMEDDS were optimized by central composite design -response surface methodology ，taking particle size and drug loading as evaluation parameters ，with the mass percentage of oil phase and the mass ratio of emulsifier to co emulsifier as factors ，and verification test was conducted . CUR/BER-SMEDDS prepared by optimized formulation were evaluated in terms of physicochemical properties，in vitro dissolution and in vitro anti-tumor effects . RESULTS The optimized formulation of CUR/BER -SMEDDS included that the oil phase was medium chain triglyceride （30.97%），the emulsifier was polyoxyl 40 hydrogenated castor oil （46.77%），the co emulsifier was polyethylene glycol 400（22.26%），and the mass ratio of emulsifier to co emulsifier was 2.10∶1. The validation experiments showed that mean particle size of CUR/BER -SMEDDS was（58.90±5.41）nm，the average drug loading was（94.94±3.87）mg/g，and the relative deviations from the predicted values were －2.90% and －0.14%，respectively. The CUR/ BER-SMEDDS prepared by optimal formulation was light yellow ，clear and transparent liquid after emulsified with water ，and its particles were spherical . The results of dissolution test in vitro showed that after SMEDDS was made ，the cumulative dissolution of CUR in artificial intestinal fluid and artificial gastric fluid and that of BER in artificial intestinal fluid were significantly higher than those of its raw material . Results of in vitro anti-tumor experiment showed that IC 50 values of CUR/BER -SMEDDS for PC -3 cells and DU -145 cells were （17.38±2.84）and（20.89±1.26）μmol/L，which were all lower than those of CUR and EBR significantly （P＜0.05）.CONCLUSIONS The optimized prepar ation process of CUR/BER -SMEDDS is stable and feasible . The drug release of CUR/BER-SMEDDS is more complete than that of single drug，and has stronger anti -prostate cancer effect in vitro .