The therapeutics of lung cancer (LC) is unsatisfactory. The pathogenesis of LC remains unclear. Protease-activated receptors (PAR) are involved in the immunoregulation. The present study aims to investigate the activation of PAR2 in regulation of the expression of EGFR and apoptosis of LC cells. The results showed that exposure to tryptase increased EGFR expression in A549 cells and suppressed the cell apoptosis. Tryptase also decreased the expression of Bax and increased Bcl-xL levels in A549 cells. We conclude that activation of PAR2 by tryptase can decrease the ratio of Bax/Bcl-xL and reduce the LC cell line, A549 cells, and apoptosis.