Abstract: Objective To find a non-invasive,efficient and non-venomous method of gene transfection by assessing whether ultrasound mediated microbubble destruction could increase human wild type p53 plasmid delivery to liver cancer.Methods Forty-eight nude mice with liver carcinoma by chemical intoxicants were divided into four groups.After p53 plasmid was injected into the femoral vein,the tumor was not irradiated by ultrasound in second harmonic mode in group 1,and was done in group 2.Ultrasonic contrast agents and plasmid DNA were administrated without ultrasound exposure in liver cancer in group 3 and with the exposure in group 4.RT-PCR and Western Blot were used to detect p53 mRNA expression in liver cancer cells.Results Expressions of p53 mRNA were detected by RT-PCR reaction in all groups.Gene expression of the liver cancer cells in group 4 was the highest and was significantly different from other groups(P＜0.05).Conclusion Ultrasound irradiation,the compounds of microbubble agent and WT-p53 have targeted inhibitive effect on the WT-p53 gene expression of hepatoma cells.