Siglec-15 (S15) is another important mechanism of tumor immune escape besides the PD-L1/PD-1 pathway and represents a new kind of immune checkpoint inhibitor. However, the associations of tumor Siglec-15 expression with clinicopathological characteristics and outcomes of non-small cell lung cancer (NSCLC), and tumor-infiltrating lymphocytes (TILs) in a tumor microenvironment (TME) have so far been unclear. A total of 324 NSCLC surgical samples on tumor microarray were used in this study for investigating the association of S15 expression with clinicopathological characteristics and overall survival (OS) as well as correlation with TILs using multiplex immunofluorescence staining and PD-L1. Results showed that the expression of S15 in adenocarcinoma was significantly higher than that in squamous cell carcinoma. S15 expression was positively correlated with CD8+ T cell density in the stroma. The expression rate of PD-L1 in lung squamous cell carcinoma was higher than that in lung adenocarcinoma. S15 expression was not associated with the prognosis of early NSCLC. The pathological mechanism of the co-expression of S15 and PD-L1 in resectable NSCLC remains to be further studied.