Tumor cells with different origins have different threshold to apoptosis. Hematopoietic (Jurkat, NCI-H929) cells and non-hematopoietic (A549, MCF-7) cells were received hyperbaric oxygen (HBO(2)) treatment from 2.5 to 3.5 atmosphere absolute (ATA) of 100% oxygen for 6h, and a significant percentage of apoptosis were shown only in hematopoietic Jurkat and NCI-H929 cells by either Annexin V or TUNEL assay. Oxidative stress was illustrated higher in HBO(2)-treated hematopoietic cells by superoxide fluorochrome detectors. HBO(2) treatment leads to caspase-3, caspase-7 activation and further cleavage of PARP within cells. Furthermore, the increased phosphorylation of p38 MAPK was demonstrated in both Jurkat and NCI-H929 cells.