Intercellular adhesion molecule‐1 (ICAM‐1) is a crucial receptor in the cell–cell interaction, a process central to the reaction to all forms of injury. Its expression is upregulated in response to a variety of inflammatory/immune mediators, including cellular stresses. The NF‐κB signalling pathway is known to be important for activation of ICAM‐1 transcription. Here we demonstrate that ICAM‐1 induction represents a new cellular response to p53 activation and that NF‐κB inhibition does not prevent the effect of p53 on ICAM‐1 expression after DNA damage. Induction of ICAM‐1 is abolished after treatment with the specific p53 inhibitor pifithrin‐α and is abrogated in p53‐deficient cell lines. Furthermore, we map two functional p53‐responsive elements to the introns of the ICAM‐1 gene, and show that they confer inducibility to p53 in a fashion similar to other p53 target genes. These results support an NF‐κB‐independent role for p53 in ICAM‐1 regulation that may link p53 to ICAM‐1 function in various physiological and pathological settings.