Objective To investigate the effects of cell-matrix adhesion on drug resistance of tumor cells. Methods MTT test was conducted to study the effects of adhesion between A549-ADR tumor cells and fibronection on sensitivity to anti-cancer drugs, the expression of bcl-2 and Bax gene protein was analyzed by flow cytometry. Results The extent of drug resistance decreased to control levels after the binding was blocked by using anti-β1 integrin antibody. The expression of bcl-2 protein was increased and the Bax protein was decreased when the tumor cell binds to fibronectin, the rate of apoptosis was also significantly decreased when the tumor cell binds to fibronectin and increased after blocked by antiβ-1 integrin antibody. Conclusion Adhesion of tumor cells with fibronectin can increase drug resistance of tumor cells probably by regulating the expression of apoptosis-related genes and the rate of apoptosis.