Objective To evaluate the safety and efficiency of erlotinib in the elderly with non-small cell lung cancer (NSCLC) and investigate the relationship of clinical characteristics with efficiency. Methods Clinical data of 43 patients with stage ⅢB/Ⅳ NSCLC who were older than 65 years and had not previously participated in erlotinib related clinical trials in our department from March 2005 to October 2010 were collected and retrospectively analyzed in this study. The correlation of survival with clinical factors was analyzed. Results Among the 43 patients, there were 12 cases of partial remission (PR), 17 of stable disease (SD), and 14 of progressive disease (PD), with an objective response rate (ORR) of 27.9%, and a disease control rate (DCR) of 67.4%. Gender (P＝0.001), tumor differentiation (P＝0.022), and smoking history (P＝0.001) were significantly correlated with ORR, while gender (P＝0.031), score of Eastern Cooperative Oncology Group (ECOG, P＝0.004), tumor differentiation (P＝0.018), smoking history (P＝0.005), and skin rash from medication (P＜0.001) were significantly correlated with DCR. The progression-free survival (PFS) was 27 weeks (95%CI: 8.32?45.7 weeks) and the overall survival (OS) was 46 weeks (95%CI: 26.7?65.3 weeks). Pathological type (P＝0.024), differentiation (P＝0.036), ECOG score (P＝0.001), and skin rash from medication (P＝0.006) had significant effects on PFS in the cohort. And, pathological type (P＝0.040), differentiation (P＝0.023), ECOG score (P＜0.001), and further chemotherapy after erlotinib (P＝0.028) were significantly effective to OS. The patients with Exon 19/21 mutations of epidermal growth factor receptor (EGFR) had obviously higher ORR (P＝0.004), DCR (P＝0.033), and PFS (46.1 vs 12.8 weeks, P＝0.004) than those without. The most common adverse effects were skin rash (51.2%) and diarrhea (23.2%). Conclusion Erlotinib is safe and effective in the treatment of Chinese elderly patients with advanced NSCLC. As for patients with good physical condition, the earlier erlotinib used, the better the prognosis will be.