Objective To investigate the expression of growth factor receptor- bound protein- 2( Grb2),matrix metalloproteinase- 3( MMP- 3),and MMP- 9 in cholangiocarcinoma and its significance. Methods The expression of Grb2,MMP- 3,and MMP- 9 in cholangiocarcinoma tissues of 47 cases and normal tissues was measured using immunohistochemistry,and the correlations of Grb2 expression with clinical pathology and MMP- 3 and MMP- 9 expression were analyzed. Comparison of continuous data was made using t test,and the correlation of Grb2 expression with MMP- 3 and MMP- 9 expression was analyzed using the multivariate linear regression model. Results The expression of Grb2 in cholangiocarcinoma tissues was significantly higher than that in normal bile duct tissues( t = 5. 935,P < 0. 001);the expression of Grb2 in cholangiocarcinoma tissues and normal bile duct tissues showed no significant correlation with age,sex,and differentiation level; the expression of Grb2 in cholangiocarcinoma tissues with lymph node or distant metastasis was significantly higher than that in cholangiocarcinoma tissues without metastasis( t = 3. 882,P = 0. 003). The expression of Grb2 was positively correlated with the expression of MMP- 3 and MMP- 9( r2= 0. 3667,P = 0. 018; r2= 0. 5133,P = 0. 007). Conclusion The expression of Grb2 in cholangiocarcinoma tissues is higher than that in normal bile duct tissues,and it is closely related to the invasion and metastasis of carcinoma. Further study shows that the expression of Grb2 is positively correlated with the expression of MMP- 3 and MMP- 9.