Abstract: OBJECTIVE To preparation wheat germ agglutinin (WGA)-conjugated EGCG-gelatin-chitosan nanoparticles， and evaluate its anti-tumor activity in vitro． METHODS EGCG-Gel-Cs nanoparticles were fabricated based on an electrostatic bonding between gelatin and chitosan. The formulation variables were optimized by Box-Behnken Design (BBD) of response surface methodology (RSM) of encapsulation efficiency (Y， %) as dependent variable. The surface of nanoparticles was then modified by glutaraldehyde-activated WGA to obtain WGA-EGCG-Gel-Cs nanoparticles. The differential scanning calorimetry was used to analyze its material phase of the drug in nanoparticles. Cell toxicity and apoptosis were employed to evaluate the anti-tumor activities. RESULTS The optimal formula was as follows: the mass ratio of Gel and Cs was 4.2， Gel and EGCG was 2.82 and the temperature was 34℃. The encapsulation efficiency of EGCG-Gel-Cs nanoparticles was (74.42±0.074)% with the particle size (264.13±6.48) nm. After modifying， the particle size increased to (389.70±9.00) nm. Simultaneously， cytotoxicity and apoptosis of WGA-EGCG-Gel-Cs nanoparticles was significantly higher than that of free EGCG. CONCLUSION Prepared WGA-EGCG-Gel-Cs nanoparticles can significantly enhance tumor cell toxicity and apoptosis of EGCG.