Objective To observe HA14-1 sensitizes Lewis lung carcinoma in mice to cyclophosphamide (CTX) and to explore its possible mechanism. Methods Forty Lewis lung carcinoma model mice were randomly divided into 4 groups:normal saline group,CTX group, HA14-1 group,CTX+HA14-1 group. After the treatment of 7 days,all of the mice were killed on the 22nd day of tumor inoculation. The tumor volume growth curve of each group was described;tumor inhibition rate was caculatued;Bcl-2,Bax,Caspase-9 protein expression levels before and after the treatment were determined by immunohistnehemistry. Results Compared to the normal saline group,HA14-1 group had no significant effect on inhibiting tumor volume,and the tumor volume in HA14-1 group increased less slowly than that of CTX group, HA14-1 group and CTX+HA14-1 group. Compared to the normal saline group, the tumor inhibition rate of HA14-1 group had no significant increase (P> 0.05),while that of CTX group and CTX + HA14-1 group increased significantly (P< 0.05);compared to the CTX group,the tumor inhibition rate of CTX + HA14-1 group increased significantly (P < 0.05). Bcl-2 protein expression levels in CTX group,HA14-1 group and CTX+HA14-1 group were lower than that in the normal saline groups compared to CTX group,Bcl-2 protein expression of CTX + HA14-1 group reduced significantly. Compared to the normal saline group,the expression levels of Bax and Caspase-9 protein in CTX group, HA14-1 group and CTX+HA14-1 group increased significantly (P< 0.05);compared to CTX group,CTX + HA14-1 group increased more significantly (P < 0.05). Conclusion HA14-1 might enhance the efficiency of CTX chemotherapy via inhibiting the expression of Bcl-2, increasing the expression of Bax and caspase-9 and promoting tumor cell apoptosis.