Premature senescence of skin human diploid fibroblasts is induced after a series of 10 sublethal exposures to UVB at 2.5 kJ/m2 with appearance of several biomarkers of cellular senescence like senescence-associated β-galactosidase activity (SA β-gal) and cell cycle arrest. Herein it is shown that the induction of UVB-induced premature senescence is associated with a transient increase of protein abundance and DNA-binding activity of p53. Silencing p53 expression with small interfering RNA (siRNA) affected the basal level of SA β-gal and proliferative potential, but did not prevent UVB-induced increase of SA β-gal and decrease of DNA synthesis. We used a senescence-specific low-density DNA array and p53 siRNA to study the mRNA abundance of 240 senescence-related genes and identified several potential p53-dependent genes differentially expressed after the repeated exposures to UVB. © 2007 Elsevier Ireland Ltd. All rights reserved.