Objective The aim of this study was to investigate the expression of MAGEA4 and EB1 proteins in lung cancer tissues and their correlation with clinicopathological features and prognosis. Methods A total of 136 patients with lung cancer in our hospital were enrolled. The expression levels of MAGEA4 and EB1 at levels of mRNA and protein were measured by real-time fluo-rescence reverse transcription and immunohistochemistry. The correlation between MAGEA4 and EB1 expression and clinical patholog-ical features,and prognosis were analyzed by χ2 test and Cox regression analysis. Results The expression of MAGEA4 and EB1 mR-NA in lung cancer tissues was higher than those in adjacent tissues(P<0. 05). The positive rates of MAGEA4 and EB1 in lung canc-er tissues were higher than those in adjacent tissues(P<0. 05). The expression of MAGEA4 and EB1 proteins in lung cancer tissues was higher than those in adjacent tissues(P<0. 05). The positive rates of MAGEA4 and EB1 proteins were not significantly correlated with age(P>0. 05),but they were related to the maximum diameter,pathological grade,TNM stage,infiltration depth,lymphatic vas-cular infiltration,lymph node metastasis and recurrence(P<0. 05). The 3-year survival rate and total survival time of MAGEA4 and EB1 negative group were significantly higher than those of MAGEA4 and EB1 positive group(P<0. 05). Lymphatic vascular infiltra-tion,lymph node metastasis,MAGEA4 positive and EB positive were independent risk factors for prognosis of patients with lung cancer (P<0. 05). Conclusion The positive expression rates of MAGEA4 and EB1 proteins in lung cancer tissues are increased,and their high expression may be related to the occurrence and development of lung cancer. Lung cancer patients with negative expression of MAGEA4 and EB1 proteins can obtain better prognosis.