Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutation is benefited from targeted therapy. There is no other superior predictive factor for targeted therapy except EGFR in the clinical. In this study, we analyzed the effect of pretreatment platelet/lymphocyte ratio (PLR) in NSCLC patients. In the present study, a total of 96 patients with EGFR mutations were included in this study. All patients received EGFR targeted therapy, until disease progression, unacceptable toxicity or other factors. The following evaluation was conducted about 3 days before initial treatment: detailed clinical history, physical examination, radiographic results, pathological diagnosis and laboratory parameters including complete blood cell counts and albumin levels. We found that pretreatment PLR is significantly associated to the PFS of NSCLC patients with EGFR targeted therapy. Patients in the PLR ≥190 group had shorter PFS than those in the PLR <190 group (P= 0.009). Furthermore, the 1-year PFS rate in the PLR ≥190 group were inferior to the low value group (P= 0.016). Multivariate analysis confirmed the role of PLR on predicting the efficacy of targeted therapy for advanced NSCLC. In addition, we found that PLR was also an predictive biomarker for grade 3/4 adverse events of diarrhea. In conclusion, high pretreatment PLR was an independent indicator for predicting a poor PFS for NSCLC patients receiving EGFR-TKIs treatment. Further studies are needed to identify the impact of PLR on results of EGFR-TKIs treatment.