Lung cancer is a complex disease involving multiple genetic and phenotypic alterations. As a histone modification enzyme, protein‑arginine deiminase type‑4 (PADI4) and its downstream signaling have been studied in the progression of a variety of types of human cancer, but data on PADI4‑mediated posttranslational modification in lung cancer are lacking. The aim of present study was to evaluate the expression of PADI4 and its associated molecular signaling in lung cancer metastasis. The results of the present study indicated that PADI4 was overexpressed in lung cancer cells, while knockdown of PADI4 could lead to attenuation of the lung cancer cell invasion and migration phenotype, which was further verified by determining the epithelial‑mesenchymal transition (EMT) marker proteins. Additionally, it was demonstrated that stable knockdown of PADI4 in A549 lung cancer cells resulted in a striking reduction of the EMT‑associated Snail1/mothers against decapentaplegic homolog 3/4 transcriptional complex, which was consistent with alterations in migratory and invasive phenotypes of A549 lung cancer cells. Therefore, PADI4‑mediated EMT transition is proposed to represent a novel mechanism underlying the epigenetic and phenotypic alterations in lung cancer cells, and the PADI4 associated signaling pathway may be a therapeutic target for treating lung cancer in a clinical setting.