In the present study, we demonstrated that (1) characteristics of ILD/IPF patients differed significantly from those of non-ILD patients; in particular, no IPF patients had EGFR mutation-positive tumors; (2) the presence of either IPF or ILD was associated with shorter PFS and OS in patients with advanced NSCLC who received chemotherapy; (3) DCR was significantly lower in ILD and IPF patients than in non-ILD patients, even those with EGFR-WT; and (4) AEs of ILD occurred more frequently after docetaxel-containing regimens than after other regimens. This evidence concerns the gene EGFR and interstitial lung disease.