Recently, β-catenin mediated immune escape mechanism has been reported in several cancers. We investigated whether β-catenin is associated with resistance to immune checkpoint inhibitor therapy in non-small cell lung cancer. Non-small cell lung cancer patients expressing high levels of β-catenin showed poor progression-free survival and overall survival after single agent anti-PD-1 therapy. They had less infiltration of CD8-positive cells and antigen-presenting cells. Microarray analysis also showed low gene expression of CD8A and IFNG. siRNA knockdown of CTNNB1 in the β-catenin-positive lung cancer cell line LK-2 tended to decrease CTNNB1 and ATF3 expression and increase CCL4 expression. The results suggest that β- catenin suppresses tumor infiltration by antigen-presenting cells and confers resistance to immune checkpoint inhibitors in non-small cell lung cancer via downregulation of CCL4 production.