BACKGROUND: Lung immune prognostic index (LIPI) was recently developed on the basis of the combination of baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH). This index was demonstrated as a specific biomarker of immune checkpoint inhibitors for non-small cell lung cancer (NSCLC). We aimed to show that LIPI may be a useful biomarker of cytotoxic chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC. METHODS: We retrospectively collected 175 wild-type EGFR adenocarcinomas, 131 NSCLCs harboring mutant EGFR and 110 squamous cell carcinomas. All patients initiated first-line cytotoxic chemotherapy or EGFR-TKI monotherapy between July 2007 and August 2017 at our hospital. These patients were divided into good, intermediate and poor LIPI groups. We compared their overall survival (OS) and progression-free survival (PFS). Multivariate analyses detected prognostic and predictive factors of OS and PFS. RESULTS: The good LIPI group survived longer than the intermediate and poor LIPI groups in wild-type EGFR adenocarcinoma (good, intermediate and poor LIPI groups: median 19.6, 11.5 and 3.3 months, P < 0.01, respectively) and mutant EGFR NSCLC (45.4, 25.6 and 15.7 months, P < 0.01). The PFS of good LIPI group was significantly longer that those of the other two groups in mutant EGFR NSCLC (16.6, 12.6 and 8.3 months, P < 0.01). The intermediate group (hazard ratio (HR) 1.49, 95% confidential interval (CI) 1.03 - 2.15, P = 0.04) of wild-type EGFR adenocarcinoma, intermediate (HR 2.30, 95% CI 1.33 - 3.99, P < 0.01) and poor (HR 2.76, 95% CI 1.03 - 7.42, P = 0.04) groups of mutant EGFR NSCLC were independent prognostic factors of poor OS. The intermediate (HR 1.57, 95% CI 1.01 - 2.44, P = 0.04) and poor (HR 2.63, 95% CI 1.14 - 6.07, P = 0.02) groups were significant prognostic factors of PFS of mutant EGFR NSCLC. CONCLUSIONS: LIPI was an independent prognostic factor of chemotherapy for adenocarcinoma with wild-type EGFR and of EGFR-TKI for NSCLC harboring mutant EGFR. Thus, LIPI was not a specific biomarker for ICI therapy, but a useful biomarker for chemotherapy and EGFR-TKI therapy in specific subsets of NSCLC.