•The ORR of PD-1 blockade was 12.3% in EGFR-mutant NSCLC.•High PD-L1 and CD8+ICs can predict response to PD-1 blockade in EGFR-mutant NSCLC.•The number of CD8+ TILs per mm2 was counted using the NDP system.•Tumors with high PD-L1 and CD8+ICs were associated with a heavy smoking history. The effectiveness of PD-1 blockade therapy in advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is limited. We investigated whether patient characteristics, PD-L1 expression, and immune cell (IC) status in the tumor microenvironment (TME) were associated with PD-1 blockade therapy outcomes. We retrospectively reviewed patients with advanced EGFR-mutant NSCLC treated with PD-1 blockade (nivolumab or pembrolizumab) between January 2016 and March 2018. The PD-L1 expression tumor proportion score (TPS) and types and distribution of ICs (CD8, PD-1, CD204, tumoral, and stromal) in the TME were analyzed. Among 57 EGFR-mutant NSCLC patients treated with PD-1 blockade, 39 patients had sufficient tissues for analyzing the TME. The overall response rate (ORR) of PD-1 blockade was 12.3%. Only tumoral CD8 positive (CD8+) IC status was significantly associated with the response (median tumoral CD8+ICs: 299/mm2 vs. 115/mm2, P < .01). Among the 6 patients with concurrent high PD-L1 expression (TPS: ≥ 50%)/high tumoral CD8+ ICs (≥ 205/mm2), 5 (83.3%) showed a response and a significantly longer progression-free survival (PFS) (PFS: 9.4M vs. 1.8M, P < .01). In contrast, none of the 7 patients with high PD-L1 expression/low tumoral CD8+ICs (<205/mm2) showed a response. Concurrent high PD-L1 expression and high tumoral CD8+ ICs could predict the response and longer PFS of PD-1 blockade therapy in EGFR-mutant patients. We investigated the tumor microenvironment (TME) of 39 epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients. Both PD-L1 expression and CD8+ TILs were necessary for the efficacy of PD-1 blockade.