Objective: To investigate the relationship of serum pulmonary surfactant-associated pretein (SP-D), transforming growth factor-α (TGF-α), matrix metalloproteinases-9 (MMP-9), tissue polypeptide speciifc antigen (TPS) and lung adenocarcinoma-related antigen (KL-6) with the effect and survival of treating advanced recurrent non-small cell lung cancer (NSCLC), and to establish a survival predication model. Methods:ELISA was applied to detect peripheral serum SP-D, TGF-α, MMP-9, TPS and KL-6 levels in 114 patients with recurrent NSCLC, and to analyze their relationship with the effect of erlotinib by combining with clinical symptoms, while one-way and multi-way analysis of variances were analyzed with Kaplan-Meier survival curve and Cox multi-way survival analysis model in order to establish the survival predication model. Results:The total effective rate and stability rate of erlotinib in 114 patients were 22.8% and 72.8%with progression-free survival (PFS) and 1-year survival rate being 5.13 months and 69.3%, respectively, and they were higher in SP-D>110 ng/mL group than in ≤110 ng/mL group (P= 0.011, P = 0.017). The stability rate in MMP-9 ≤ 535 ng/mL and TPS 535 ng/mL (P=0.009) and TPS≥80 U/L groups (P=0.002) respectively, while mPFS in SP-D>110 ng/mL, MMP-9≤535 ng/mL, KL-6