The aim of this study was to observe the clinical efficacy and side effects of verapamil combined with antitumor drugs via Pleural Catheter Perfusion (PCC). From December 2004 to December 2014, a total of 79 patients with Malignant Pleural Effusion (MPE) were randomly divided into the control group (C, n=37) and the treatment group (T, n=42). Group C was perfused with interleukin-2, 5-fluorouracil, and cisplatin, and group T was perfused with verapamil, interleukin-2, 5-fluorouracil, and cisplatin. The post-treatment clinical efficacy, side effects, median survival time, and overall survival were evaluated and compared between the two groups. After the treatment, the efficacy rate (CR+PR) of group C was 51.35%, and that of group T was 80.95%. There was significant difference between the two groups (P<0.05); the median survival time of group C was 4 months, and that of group T was 13 months. There was significant difference between the two groups (P<0.01). Grades I~II side effects appeared in group T after the treatment, but released in short period, and showed no significant difference with group C (P>0.05). No significant side effect in the cardiovascular system appeared. This study can improve the clinical treatment of MPE and prolong the survival time.