OBJECTIVE： To observe the efficacy and safety of oxaliplatin combined with thymosin in the treatment of lung cancer with malignant pleural effusion. METHODS： 120 lung cancer patients with malignant pleural effusion were randomly divided into control group （60 cases） and observation group （60 cases）. All patients received chest microtubules drainage， then thoracic cavity drug infusion after clean effusion drainage verified by B ultrasound， 10 mg Loratadine tablet was orally given before going to bed 1 d before drug infusion， for 1 week； 25 mg Promethazine hydrochloride injection was intramuscularly injected 30 min before drug infusion for allergy prevention， 20 mg metoclopramide for gastrointestinal reaction prevention， 10 mg dexamethasone and 10 ml 2％  lidocaine， adding into 10 ml 0.9％ Sodium chloride solution， injected to thoracic cavity by drainage tube to prevent and relief chest pain， fever， and other pleural reaction symptoms. Based on it， control group was injected 100 mg/m2 Oxaliplatin for injection to thoracic cavity by drainage tube. Observation group was additionally given 300 mg Thymosin injection， to thoracic cavity by drainage tube. Pleural effusion was drained after 2 d. Once every week in 2 groups， 4-week was regarded as 1 coure，and it lasted 2 courses. Clinical efficacy， clinical benefit rate， and serum T lymphocyte subsets （CD3+，CD4+，CD8+）， inflammatory cytokines levels [interleukin （IL）-6， tumor necrosis factor （TNF）-α）] before and after treatment in 2 groups were observed， survival status and the incidence of toxicity reactions were followed-up. RESULTS： The objective response rate， disease control rate， clinical benefit rate， survival rate in observation group were significantly higher than control group， the incidence of toxicity reactions was significantly lower than control group， the differences were statistically significant （P＜0.05）. After treatment， CD3+， CD4+， CD8+ levels in observation group were significantly lower than before， and observation group was lower than control group， the differences were statistically significant （P＜0.05），there were no significant differences in CD3+，CD4+，CD8+ levels before and after treatment in 2 groups（P＞0.05）. CONCLUSIONS： Oxaliplatin combined with thymosin can improve efficacy in the treatment of lung cancer with malignant pleural effusion， prolong survival period， improve survival quality and reduce the incidence of toxicity reactions.