Objective: To assess the value of tumor marker SP70 level, liquid based cytology examination and combining two methods in predicting lung adenocarcinoma in pleural effusion. Methods: A total of 39 patients in the Affiliated Hospital of Xuzhou Medical University from November 2018 to March 2019 were retrospectively reviewed, including 27 patients with lung adenocarcinoma in pleural effusion and 12 patients with benign pleural effusion. The pleural effusion before radiochemotherapy was collected and detected by liquid-based cytology, meanwhile, SP70 level was detected by the method of ELISA. Sensitive, specificity and accuracy were applied to assess the diagnosis value of two methods in predicting lung adenocarcinoma in pleural effusion. Results: ROC curve for SP70 level in pleural effusion was applied and under curve area was calculated. SP70>9.73 ng/mL helped to predicting lung adenocarcinoma in pleural effusion with the sensitivity of 70.4%, specificity of 91.7%. The area under ROC curve was 0.824. The accuracy and sensitivity of SP70 combined with liquid based cytology were 89.7% and 81.4%, both higher than liquid based cytology alone. The difference was statistically significant (P<0.05). Conclusion: Liquid based cytology and SP70 level were useful in predicting lung adenocarcinoma in pleural effusion to a certain degree. Combining 2 methods could improve the sensitivity and accuracy.