Abstract: Objective To evaluate the efficacy and safety of pemetrexed combined with cisplatin for metastatic osteosarcoma patients. Methods We collected 18 osteosarcoma patients with lung metastasis with failed first-line chemotherapy, 18 males and 14 females. Median age was 20 years old, and Karnofsky performance status(KPS) score was ≥70. The patients received pemetrexed 500mg/m2 on day 1 and cisplatin 80-100 mg/m2 on day 1-2 by intravenous infusion, 21 days as a cycle. Efficacy and toxicity were evaluated after 2 cycles. Results Totally 18 patients could be evaluated, with 0 case of CR or PR, 1 case of minimal response(MR), 7 cases of stable disease(SD) and 10 cases of progression disease(PD). Disease control rate was 44.4% (8/18). Median progression-free survival and overall survival time were 9.0 weeks (95% CI: 5-13 weeks) and 12.0 months (95%CI: 9-16 months), respectively. The common adverse effects were digestive tract reaction (50.0%), anemia (44.4%) and fatigue (38.9%), which were apparently relieved after symptomatic treatments. Conclusion Pemetrexed combined with cisplatin have certain efficacy for osteosarcoma patients with lung metastasis, with well tolerance and low incidence of adverse reactions.