We provide evidence for modulation of p53 signalling at the p21 promoter, mediated by LRH-1, and propose a model in which LRH-1, in complex with co-repressors, suppresses p53 action at the p21 gene, allowing CRC cells to evade cell cycle arrest mediated by p21. The gene discussed is NR5A2; the disease is colorectal carcinoma.