Trastuzumab is the first molecular targeting drug to increase the overall survival rate in advanced gastriccancer. However, it has also been found that a high intrinsic or primary trastuzumab resistance exists in someproportion of gastric cancer patients. In order to explore the mechanism of resistance to trastuzumab, firstlywe investigated the expression of MUC1 (membrane-type mucin 1) in gastric cancer cells and its relationshipwith drug-resistance. Then using gene-silencing, we transfected a siRNA of MUC1 into drug-resistant cells.The results showed the MKN45 gastric cell line to be resistant to trastuzumab, mRNA and protein expressionof MUC1 being significantly upregulated. After transfection of MUC1 siRNA, protein expression of MUC1in MKN45cells was significantly reduced. Compared with the junk transfection and blank control groups, thesensitivity to trastuzumab under MUC1 siRNA conditions was significantly increased. These results imply thatHER2-positive gastric cancer cell MKN45 is resistant to trastuzumab and this resistance can be cancelled bysilencing expression of the MUC1 gene.