Abstract: Objective To observe the effect of intrapleural gemcitabine combined with bevacizumab in the treatment of pleural effusion of lung cancer. Methods Twenty-eight patients with non-squamous non-small cell lung cancer with malignant pleural effusion were enrolled in our study from September 2016 to March 2017. They were divided into two groups according to the random number table method. All patients received systemic chemotherapy with gemcitabine 1 000 mg/m² (d1 & d8) plus carboplatin 400 mg/m² (d1), and then patients in group A (observation group) were treated with intrapleural gemcitabine (250 mg/m²) plus bevacizumab (5 mg/kg), while group B (control group) with gemcitabine (250 mg/m²) alone. The treatment was performed for 4 cycles (3 weeks for 1 cycle). The changes of pleural effusion, drug adverse reactions and gemcitabine drug concentration in the two groups were observed after treatment. Results There was no significant difference in baseline data such as gender, age, smoking habit, tumor stage and KPS score between the two groups. The objective response rate (ORR) of observation group was significantly higher than that of control group (83.3% vs 40.9%, P=0.008). The incidence of hypertension in the observation group was significantly higher than that in the control group (58.3% vs 0, P=0.000); In the observation group, the incidences of neutropenia (58.3% vs 50.0%, P=0.571) and diarrhea (16.7% vs 0, P=0.139) were slightly higher than those of the control group, while the incidences of nausea and vomiting (29.2% vs 36.4%, P=0.603), epistaxis (62.5% vs 68.2%, P=0.686) were slightly lower than those of control group, but the differences were not statistically significant. After 12 hours of thoracic administration, the concentration of gemcitabine in the chest cavity of the observation group was significantly higher than that of the control group (1.5±0.38μg/ml vs 1.25±0.16μg/ml, P=0.04), which prolonged gemcitabine dwelling time in the thorax. Conclusion Intrapleural bevacizumab combined with gemcitabine can control malignant pleural effusion more effectively, and increase duration of drug action of gemcitabine.