Abstract: Objective To observe the effects of suicide gene system HSV-TK/GCV combined with sonodynamic therapy on human lung cancer cell NCI-446 in vitro. Methods NCI-446/TK containing HSV-TK gene has been screened by the method of fluorescence and RT-PCR.MTT detected the damage effects of cells after NCI-446/TK treated with different concentrations of GCV.And bystander effect was also measured through mixed different concentrations of NCI-446 and NCI-446/TK. Meanwhile,combining HSV-TK/GCV suicide gene system and sonodynomic theragy,cell survival rate was tested by MTT,in addition,cell cycle and apoptotic rate were tested by Flow cytometry. Results With 0.2 mg/L of GCV,the growth of NCI-446/TK was inhibited significantly (P<0.01).With increased GCV,the inhibitory effect became obviously.When 10% NCI-446/TK in mixed cells,there was 46％ total cells were inhibited.And also the inhibitory effect increased with increasing proportion of NCI-446/TK.After therapeutic alliance with suicide gene system HSV-TK/GCV and SDT,cell survival ratio was significantly lower than the groups of single treatment and the proportion of cells in G0/G1stage,as well as apoptotic rate,were also higher than the groups of single treatment. Conclusion The lethal effect of HSV-TK/GCV suicide gene system was enhanced with increase of GCV concentration and bystander effect was also significant.When combined with SDT,the effect was better than a single treatment group.