Abstract: ObjectiveTo explore the clinical pathology effect of gene mutation of p53 in lung cancer on TSG101/MDM2 signal passway. MethodsImmunohistochemical method was adopted to detect the expression of TSG101，MDM2 and p53 in lung cancer tissues of 185 cases.PCR-SSCP was used to detect the gene mutation of p53.Western blot method was adopted to detect the expression of TSG101 in tumor tissues and normal tissues. Results （1）The overall positive rate of p53 protein in the group of cancer was 80.54%(149/185).The result of PCR-SSCP showed that the overall mutation rate was 56.67%(17/30).The expression of p53 protein had correlation with the stages of pathology and the lymph node(P<0.05).The low expression rate of TSG101 protein was 58.92%(109/185).The result of Western blot showed that the expression of TSG101 in the group of cancer tissues was significantly lower than that in the control group(P<0.05).The expression of TSG101 protein had correlation with the stages of pathology，differentiation and lymph node metastasis(P<0.05).The excess expression rate of MDM2 protein was 77.84%(144/185).The expression of MDM2 protein had correlation with the stages of surgery pathology and lymph node metastasis(P<0.05).（2）There were 76 cases of TSG101 positive and 139 cases of MDM2 positive in the 149 cases p53 positive, respectively.There were 3 cases of TSG101 negative and 31 cases of MDM2 negative in the 36 cases of p53 negative, respectively.The altogether expression rate was 91.89%. Conclusion (1)The up-regulated expression of p53/MDM2 and decline of TSG101 have correlation with the occurrence of lung cancer and its biology behavior.(2) When p53 gene is mutation, the expression of TSG101 and MDM2 is negative correlation.