Abstract <p><b>Objective:</b> Depending on the intensity of the stress impact and the extent of damage it causes, normal somatic cells can initiate signaling cascades aimed at repairing damage and maintaining functionality, establishing an irreversible block of proliferation and entering senescence state, or inducing death. The key molecular regulator of all stress signaling cascades is protein p53, which status in the cell is controlled by various post-translational modifications. One of tsuch modification that facilitates transcriptional activation of p53 is its methylation by lysine-specific methyltransferase SETD7. <b>Methods:</b> The objective of this study was to examine the role of SETD7 in mediating p53-dependent responses of normal human stromal cells exposed to lethal and sublethal doses of oxidative stress. <b>Results and Discussion:</b> Our results indicate that stromal cells respond to sublethal oxidative stress by initiating senescence, and to lethal oxidative stress by initiating apoptosis. The development of both stress reactions is accompanied by activation of p53. Notably, stromal cells with SETD7 knockout do not differ from control ones, either in their normal state or under oxidative stress. Thus, under the influence of sublethal doses of the oxidizer, knockout cells demonstrate signs of senescence, while following treatment with its lethal doses, the cells undergo apoptotic death. Importantly, in both cases the dynamics and intensity of p53 activation were comparable between control and knockout cells. <b>Conclusions:</b> Thus, our findings suggest that SETD7 is not an essential molecular component for the activation of p53-dependent stress responses in normal human stromal cells exposed to oxidative stress.</p>