ObjectiveTo evaluate the effect of Fuzheng Kang'ai Formula (?????, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations.MethodsA randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed.ResultsNo patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05).ConclusionPatients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.