Objective: The aim of the study was,(1) to observe the short-term efficacy and adverse reactions of icotinib hydrochloride on the treatment of advanced non-small cell lung cancer(NSCLC);(2) to explore whether there is difference in the efficacy of icotinib hydrochloride among the subgroups of sex, age, smoking history, classification of CEA, histological type, multi-line treatment and PS score. Methods: The study was conducted to collect 138 patients taking icotinib hydrochloride with advanced non-small cell lung cancer in hospitals of Dalian(China) from September 1st 2011 to June 14th 2012. All patients had taken icotinib hydrochloride(125 mg three times a day) until the disease was progressed or the adverse reactions could not be tolerated. During the period of taking it, other anti-tumor treatments were forbidden. We observed the symptoms, such as cough, short breath, hemoptysis, pain. The objective efficacy was evaluated by RECIST criteria, and the adverse reactions related to the treatment was assessed on the basis of NCI-CTC 3.0. Results: Of all patients, CR was 1(0.7%), PR was 59(42.8%), SD was 37(26.8%), PD was 41(29.7%). And ORR was 43.5%(60/138), DCR 70.3%(97/138). The DCR of females was 83.5%(71/85) versus 49.1%(26/53) of males. The difference of ORR and DCR between the two subgroups had statistical significance(χ2 = 8.065, P = 0.05; χ2 = 18.577, P = 0.000). The difference of ORR and DCR between the subgroups of patients after or before 70 years old had no statistical significance. The difference of ORR and DCR between the subgroups of smoking and non-smoking had statistical significance(χ2 = 8.492; χ2 = 13.602). The difference of ORR and DCR between the CEA subgroups had statistical significance(χ2 = 14.141; χ2 = 14.160), showed 81 patients with abnormal CEA before the treatment with ORR 56.8.0%(46/81), DCR 81.5%(66/81); 57 patients of normal CEA before the treatment with ORR 24.6%(14/57), DCR 52.6%(30/57). The 36 patients(26.1%) using icotinib hydrochloride as the first-line treatment, 78 patients(56.5%) using icotinib hydrochloride as the second-line, 20 patients(14.5%) using icotinib hydrochloride as the third-line, and 4 patients(2.9%) with tyrosine kinase inhibitor(TKI) resistance, there was statistical difference of DCR among the multi-groups above(χ2 = 11.734, P = 0.008). ORR was 31.1%(14/45) versus DCR 53.3%(24/45) in 45 patients with PS 3–4 points, and ORR was 49.4%(46/93) versus DCR 78.5%(73/93) in 93 patients with PS 0–2 points, and there was statistical difference(χ2 = 4.156; χ2 = 9.149). The main adverse reactions were rash(26.8%), diarrhea(13.8%), mild liver function abnormal(10.9%). Conclusion: The short-term efficacy of icotinib hydrochloride on the treatment of advanced NSCLC is positive, and the relevant adverse reactions are mild. The efficacy is better when the patient is female, non-smoker, treated as first-line, with higher CEA before treatment and lower PS scores.