Abstract: Objective To observe the effciency of combined irinotecan (CPT-11) and oxaliplation (LOHP) third-line chemotherapy in advanced gastric cancer patients and its adverse reactions. Methods Clinical data about 31 advanced gastric cancer patients who received combined CPT-11 and LOHP third-line chemotherapy in our hospital from July 2007 to July 2012 were retrospectively analyzed. The patients were treated with intravenous CPT-11 (180 mg/m²) and LOHP (85 mg/m²), respectively, with 21 days as a cycle. Their adverse reactions were assessed after each cycle according to the NCI-CTCAE (version 3.0) and the efficiency of the combined therapy was assessed after 2 cycles according to the RECIST (version 1.1). The effective rate of the combined therapy and the incidence of adverse reactions were calculated. The survival rate of patients was analyzed using the Kaplan–Meier product limit method. Results Of 31 patients, 1 (3.2%) was completely remitted, 6 (19.4%) were partially remitted, 19 (61.3%) became stable, and 5 (16.1%) had progression with an overall response rate (CR+PR) of 22.6% and a disease control rate (CR+PR+SD) of 83.9%. The progression-free survival (PFS) time was 5.0 months (95% CI: 3.2-6.8) and the median overall survival (OS) time was 7.8 months (95% CI: 6.7-8.9). Severe adverse reactions included neutropenia in 5 patients (16.1%), leucopenia in 6 patients (19.4%), thrombocytopenia in 3 patients (9.7%), anaemia in 2 patients (6.5%) and diarrhea in 2 patients (6.5%). No chemotherapy-related death occurred. Conclusion The short-term efficiency of combined CPT-11 and LOHP third-line chemotherapy is good and its adverse reactions are tolerable in advanced gastric cancer patients.