The TOE1 gene was discovered as a target of the Egr1 transcription factor that participates in cell growth regulation through the upregulation of p21 and a cell cycle delay at the G2/M phase. We report here that TOE1 is able to bind to the p53 tumor suppressor protein, specifically interacting with the C terminal tetramerization domain of p53. We have further characterized this interaction through determination of binding kinetics using nanoporous optical interferometry and demonstrated that this interaction is capable of enhancing the transcriptional activity of p53-dependent gene targets. These results suggest a mechanistic role for TOE1 as a co-regulator of p53.