The NSCLC patients who experienced good clinical responses to an EGFR-TKI will inevitably develop acquired resistance. A great deal of research are focusing on this issue. Arsenic trioxide showed efficacy and safety in acute promyelocytic leukemia, multiple myeloma and other solid tumors. Moreover, preclinical studies showed arsenic trioxide can reduce the resistance of tumor cells to chemotherapy and TKIs.

Inclusion Criteria:

• Histologically or cytologically confirmed stage IIIB/IV lung cancer with EGFR mutation
• Progressed after platinum-based chemotherapy
• The last anti-tumor therapy before entering this study must be gefitinib, erlotinib or icotinib, and the duration for tumor response must be no less than 4 months, or the duration for stable disease must be no less than 6 months
• With a measurable disease with conventional CT) according to RECIST Criteria
• WHO performance status(PS)<= 2
• N>=1.5×109/L, Plt>=1.0×109/L,Hb>=9g/dL; AST&ALT should <2.5ULN(without liver metastasis) or <5ULN(with liver metastasis).TBIL<=1.5ULN.
• Signed and dated informed consent before the start of specific protocol procedures.

Exclusion Criteria:

• Allergic to icotinib or arsenic trioxide.
• Patients with metastatic brain tumors with symptoms.
• Severe systemic disease out of control such as unstable or uncompensated respiratory,cardiac,liver,renal diseases.