OBJECTIVE： To provide theoretical basis for R&D of chalcone anti-tumor drugs by studying 3D-QSAR of chalcone compounds inhibiting the growth of human breast tumor cell MCF-7. METHODS： The structure and activity value （pIC50） of 55 chalcone compounds were analyzed. After molecular alignment， comparative molecular field analysis （CoMFA） was used to investigate three dimensional field and electrostatic field， and comparative molecular similarity indices analysis （CoMSIA） was used to investigate steric field， electrostatic field， hydrophobic field， hydrogen bond donor field and hydrogen bond receptor field of chemical compound. Finally， optimal substituent group was confirmed and predicted. RESULTS： CoMFA model showed the effects of steric field and electrostatic field of the compound on its activity； CoMSIA model showed the effects of hydrophobic field， electrostatic field and hydrogen bond acceptor field of the compound on its activity. After molecular alignment， hydrophilic group introduced around R1， R2 substituent group of public frame， and the group with negative charge introduced in R1， R4 substituent group， steric hindrance of R2 substituent group reduced and positive charge introduced in R2 and R4， can significantly increase the activity of chalcone compounds. 2 new compounds were designed according to above results， pIC50 of them were 5.538， 5.589 （CoMFA model） and 5.552， 5.628 （CoMSIA method）. CONCLUSIONS： 3D-QSAR can accurately analyze the structural character of chalcone compounds inhibiting the growth activity of MCF-7 cells and provide theoretic direction for new drug R&D.