Cell senescence is characterized by senescent morphology and permanent loss of proliferative potential. HDAC inhibitors (HDACI) induce senescence and/or apoptosis in many types of tumor cells. Here, we studied the role of cyclin-kinase inhibitor p21^waf1(Cdkn1n gene) in cell cycle arrest,   senescence markers (cell hypertrophy, SA-bGal staining and accumulation of gH2AX foci) in p21^Waf1+/+ versus p21^Waf1-/- mouse embryonic fibroblast cells transformed with E1A and cHa-Ras oncogenes (mERas). While short treatment with the HDACI sodium butyrate (NaB) induced a reversible G1 cell cycle arrest in both parental and p21^Waf1-/- cells, long-term treatment led to dramatic changes in p21^Waf1+/+ cells only: cell cycle arrest became irreversible and cells become hypertrophic,  SA-bGal-positive and accumulated gH2AX foci associated with mTORC1 activation. The p21^Waf1+/+ cells lost their ability to migrate into the wound and through a porous membrane. Suppression of migration was accompanied by accumulation of vinculin-staining focal adhesions and Ser3-phosphorylation of cofilin, incapable for F-actin depolymerization. In contrast, the knockout of the p21^Waf1 abolished most of the features of NaB-induced senescence, including irreversibility of cell cycle arrest, hypertrophy, additional focal adhesions and block of migration, gH2AX foci accumulation and SA-bGal staining. Rapamycin, a specific inhibitor of mTORC1 kinase, decreased cellular hypertrophy, canceled coffilin phosphorylation and partially  restored cell migration in p21^Waf1+/+ cells. Taken together, our data indicate a new role of p21^Waf1 in cell senescence, which may be connected not with execution of cell cycle arrest, but also with the development of mTOR-dependent markers of cellular senescence.