The p53 protein is a tumour suppressor frequently mutated incancer. Majority of these mutations are missense mutations, with six of them occurring more frequently than others. One of them is the R273H mutation and over the years, it has been shown to confer oncogenic gain-of-function properties to the p53 protein. Studies have shown that mutant p53^R273H enhances cellular response to TNFa and increases cellular invasion. Additionally, p53^R273H also upregulates the phosphoinositide 3-kinase (PI3K)/AKT pathway to drive cancer invasion. However, a link between p53^R273H, TNFa stimulation and PI3K/AKT pathway activation has not been established. Here, we identified an important mediator of the PI3K/AKT pathway to be a binding partner of p53^R273H. We also found that its activity is increased by p53^R273H, leading to activation of the NF-kB pathway and induction of proinflammatory genes. This was further enhanced upon TNFa stimulation. We discovered that PRIMA-1^Met treatment could disrupt their interaction and dampen TNFa response.