Objective To observe the clinical efficacy and safety of high-frequency diathermic therapy and intra-thoracic chemotherapy with recombinant endostar combined with cisplatin in treatment of malignant pleural effusion. Methods A total of 48 patients with malignant pleural effusion diagnosed in the First People ' s Hospital of Guiyang from September 2014 to September 2016 were randomly divided into observation group and control group with envelope method. Twenty-four patients in observation group were received high-frequency diathermic therapy and cisplation 60 mg/m2 combined with endostar 25-30 mg/m2 intra-thoracic chemotherapy. Twenty-four patients in control group were treated with high-frequency diathermic therapy and single cisplation 60 mg/m2 intra-thoracic chemotherapy. The patients were karnofsky performance scores ≥70, cooperate with intravenous systemic chemotherapy, every 21 days for a total of two or three cycles. High frequency diathermic therapy was administered twice a week for 3 weeks 30 minutes after intra-thoracic chemotherapy,treatment time of 60 minutes every time. Chi-squared test were selected to evaluate the clinical efficacy and quality of life and adverse and toxic responses, respectively. The paired samplest test were selected to evaluate the variation of tumor markers in hydrothorax of the two groups pretherapy and post-treatment. Results In 24 patients of observation group, 2 patients were complete remission (CR), 17 patients were partial remission (PR), 4 patients were disease stable (SD), 1 patient was disease progression (PD), and the objective response rate (ORR) (CR+PR) was 79.2 ％. In 24 patients of control group, 0 patient was CR, 12 patients were PR, 7 patients were SD, 5 patients were PD, and the ORR was 50.0％, there was significant difference in ORR between the two groups (χ 2 = 4.463, P = 0.035). Karnofsky performance scores in observation group was higher than that in control group after treatment, patients with clinical benefit rate was 79.2 ％ vs. 54.2 ％, but the difference in life quality between the two groups was no statistically significant (χ2=3.375, P=0.066). There was no significant difference in adverse reactions between the two groups (P>0.05). The tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA-125), carbohydrate antigen 199 (CA-199), cytokeratin 19 fragments (CYFRA21-1) and neuron-specific enolase (NSE) in hydrothorax of the two groups were reduced by the treatment, except for the difference of CYFRA21-1 between the two group was not statistically significant (P= 0.161), the changes of the other 3 indicators in the observation group before and after treatment were greater than those in the control group (all P< 0.05). Conclusions High-frequency diathermic therapy and intra-thoracic chemotherapy with single cisplatin are effective in treating patients with malignant pleural effusion, and is more superior when combined with endostar. Additionally, the combination of the above two drugs has synergistic action and better safety, deserves to be further promoted in clinic.