Objectives : The purpose of the study is to examine the apoptotic effects of Pseudomonas aeruginosa exotoxin A(PEA) in squamous cell carcinoma(SCC) 25 cells. Methods : Cell growth reduction and apoptosis induced by PEA were confirmed by WST-1 assay, Hoechst 33258 staining, flow cytometry analysis, and Western blot assay. Results : The PEA treatment decreased the cell viability in a dose and time dependent manner: control; $100{pm}0^e$(p<0.01), 0.1875 nM; $87{pm}4.36^d$(p<0.01), 0.375 nM; $82{pm}0.58^d$(p<0.01), 0.75 nM; $72{pm}1.67^c$(p<0.01), 1.5 nM; $51{pm}1.53^{bc}$(p<0.01), 7.5 nM; $31{pm}1.20^{ab}$(p<0.01), 15 nM; $26{pm}0.67^a$(p<0.01), control; $100{pm}0^a$(p<0.05), 24 h; $51{pm}1.53^b$(p<0.05), 48 h; $16{pm}0.5^c$(p<0.05), 72 h; $12{pm}1.67^d$%(p<0.05). The PEA was observed on SCC 25 cells with the half maximal inhibitory concentration(IC50) value of 1.5 nM at 24 hours. The PEA treated SCC 25 cells demonstrated several types of apoptotic indications, such as nuclear condensation, the increase of sub G1, and the cleavage of PARP-1 and DFF 45. Conclusions : PEA showed anti-cancer activity against SCC 25 cells via apoptosis. PEA may potentially contribute to human oral cancer treatment.