Objective: To compare the clinical effects and safety pemetrexed combined with platinum and other platinum duplex regimens for treating non-drive gene positive advanced lung adenocarcinoma. Methods: 120 cases of non-drive gene positive advanced lung adenocarcinoma patients were divided into experimental group (n=55) and control group (n=65) according to treatment. The patients in experimetal group were treated with pemetrexed combined with platinum regimens, while the patients in control group were treated with TP(taxol+cisplatin) / DP(docetaxel+cisplatin) / GP(gemcitabine+cisplatin) chemotherapy regimens. The curative effects and safety of patients in 2 groups were evaluated after 4 treatment cycles. Results: The overall response rate (ORR), disease control rate (DCR), overall survival (OS), 1 year survival rate of patients in experimental group were obviously higher than control group (P<0.05). The incidence rate of thrombocytopenia, leukopenia and anemia of patients in experimental group were obviously lower than control group (P<0.05). Conclusions: Compared with TP/DP/GP regimen, treating non-drive gene positive advanced lung adenocarcinoma with PC regimen can get more significant effects and less adverse reactions, so it is worthy to be popularized in clinic.