Abstract: Objective To assess the value of changes of p53 gene、K-ras gene in the lung cancer and two genes combined together for the detection of lung cancer. Methods In 59 case lung cancer cancer cases and 14 cases with benign respiratory diseases.PCR-SSCR-AgNO3 staining method was applied to detect the mutations of 5～8 exon of p53 gene;The mutations of first exon of K-ras gene were also detected by PCR-RFLP technique.Their relevant sputum were also studied. Results The frequency of p53、alteration was 37.3% while the frequency of K-ras alteration in adenocarcinema was 48.0%.These frequency of alteration in the sputum were 33.8% and 44.0%.No p53 and K-ras gene mutations was detected in the specimens of benign respiratory diseases.The changes of p53、K-ras gene showed no difference in the biopsy specimens and relevant sputum.The mutation rate of p53 and K-ras in smokers were 48.7% and 68.5%,while in non-smokers were 15.0% and 11.1%,P<0.01.The value of these two markers using together for detection of lung cancer was also assessed.The result showed that the sensitivity of two markers combined(54.2%) was obviously higher than that of single gene detection. Conclusion The changes of p53,K-ras are common in lung cancer.The genetic changes of sputum can reflect that of lung biopsy.The detection of several kinds of molecular genetic markers together in sputum may help the diagnosis of lung cancer.