Abstract: Although p21-activated kinase 2 (PAK2) is an essential serine/threonine protein kinase, its role in the progression of lung squamous cell carcinoma (LUSC) has yet to be fully understood. We analyzed PAK2 mRNA levels, DNA copy numbers, and protein levels by quantitative reverse transcription-PCR and immunohistochemical staining in both human LUSC tissues and adjacent normal tissues. Then, we performed colony formation assays, cell counting kit-8 assays, Matrigel invasion assays, wound healing assays, and xenograft models in nude mice to investigate the functions of PAK2 in LUSC progression. We demonstrated that PAK2 mRNA levels, DNA copy numbers, and protein levels were upregulated in human LUSC tissues, compared with adjacent normal tissues. Additionally, higher PAK2 expression was associated with poorer prognosis in LUSC patients. In the in vitro study, we found that PAK2 promoted cell growth, migration, invasion, epithelial-mesenchymal transition, and cell morphology regulation in LUSC cells. Mechanistically, PAK2 promoted tumor cell proliferation, migration, and invasion by regulating actin dynamics through the LIMK1/cofilin signaling pathway. Our findings indicate that the PAK2/LIMK1/cofilin signaling pathway may serve as a potential clinical marker and therapeutic target for LUSC.