Abstract: Objective To evaluate the efficacy and prognostic factors of irinotecan plus cisplatin for patients with carcinoma of unknown primary site (CUP). Methods Seventy-two patients were enrolled. Two patients were not treated with chemotherapy. Seventy cases were treated by irinotecan combined with cisplatin, irinotecan 180 mg/m2, intravenously, d1 and cisplatin 75 mg/m2, d1-d3, intravenously, 21 days for one cycle. Results Sixty-six patients were evaluable for the response. Objective response rate (CR+PR) was 42.4% with 4 complete response(CR), 24 partial response(PR), 16 stable disease(SD) and 22 progressive diseases(PD). The median time to disease progression (TTP) was 4.5 months and the median overall survival (OS) was 10.3 months. The 1- and 2-year survival rates were 38.9% and 8.3%, respectively. The most frequent side effects included neutropenia, nausea and vomiting. The factors of performance status (PS) 0-1, number of metastatic sites <3 and presence of lymphadenopathy were signifi cantly associated with the longer overall survival (P <0.05). Conclusion These results indicate that the combination of irinotecan plus cisplatin is an effective and safe regimen for CUP patients. The PS, number of metastatic sites and presence of lymphadenopathy are only important prognostic factors for CUP.