The aim of this study was to evaluate the safety and effectiveness of erlotinib plus DC/CIK in maintenance therapy of advanced non-small cell lung cancer. After 4 cycles of the 2-drug regimen treatment with platinum, the 54 patients with non-small cell lung cancer in phase IIIb or IV reached stable or beyond stable stages. The patients were then randomly divided into 2 groups. One group was treated with erlotinib therapy (erlotinib group), and the other was treated with DC/CIK plus erlotinib (DC/CIK plus erlotinib group). The progression-free survival of the erlotinib group and the DC/CIK plus erlotinib group was 3.98 months (95% CI, 3.56-4.40) and 5.02 months (95% CI, 4.32-5.72) (P=0.002), respectively. The median overall survival of the erlotinib group and the DC/CIK plus erlotinib group was 9.9 months (95% CI, 9.1-10.6) and 10.5 months (95% CI, 9.6-11.4) (P=0.29), respectively. The levels of CD3, CD4, and CD8 were significantly different before and after the treatment in the DC/CIK plus erlotinib group, but not in the erlotinib group. There was no significant difference in toxicity between the 2 groups. In conclusion, there was no statistically significant difference in overall survival between DC/CIK plus erlotinib and erlotinib as maintenance therapy. DC/CIK plus erlotinib was well tolerated with a manageable safety profile.