OBJECTIVE： To compare the clinical efficacy of erlotinib between late non-small cell lung cancer （NSCLC） patients with epidermal growth factor receptor （EGFR） exon 19 mutation and those with exon 21 mutation. METHODS： Late NSCLC patients with EGFR mutation positive enrolled in our hospital during Oct. 2013-Nov. 2014 were selected. Patients with EGFR exon 19 Del mutant were regarded as group A， and patients with exon 21 L858R mutant were regarded as group B， 45 cases in each group. All patients were orally administered with Erlotinib hydrochloride tablets till progression. The disease control rate （DCR）， median survival time （MST）， median time to progress （mTTP）， one-year survival rate and incidence of adverse reactions in 2 groups were compared. RESULTS： The DCR （93.02％） and one-year survival rate （81.40％） in group A were obviously higher than that of group B （72.09％， 60.47％） （P＜0.05）， MST [（15.47±2.87） month] and mTTP [（182.00±8.24） d] were obviously longer than that of group B [（12.55±2.92） month， （162.00±7.22） d] （P＜0.01）. There was no statistical significance in the incidence of adverse reactions in 2 groups （P＞0.05）， and there were no severe adverse reactions. CONCLUSIONS： For patients with late NSCLC， erlotinib shows superior efficacy in patients with EGFR exon 19 mutation to patients with EGFR exon 21 mutation.