ING proteins are putative tumour suppressor proteins linked to the p53 pathway and to the chromatin modification machinery. Here, we have analysed the role of the products of the murine Ing1 locus in cellular tumour-protective responses, using mouse primary fibroblasts where the Ing1 locus has been inactivated by the integration of a ßgeo cassette. We show that Ing1-deficient MEFs display a defective senescence-like antiproliferative response against oncogenic Ras, affecting several senescence-specific markers. This phenotype is accompanied by a reduced accumulation of p53, which can be explained by the reduced basal p53 protein stability in the Ing1-deficient background. Ing1 deficiency also results in defects in the appearance of heterochromatic marks upon expression of oncogenic Ras, suggestive of impaired heterochromatin formation during oncogene-induced senescence. Our results support an important role for the Ing1 locus in protection against oncogenic stress in vivo, both as a mediator of p53 activation, and as a regulator of chromatin remodelling processes.