Mutations in the tumour suppressor gene, TP53 occur in more than 50% of human cancers. Mutant p53 proteins not only lose their tumour suppressive capacities, but they also gain oncogenic functions broadly referred to as gain of function (GOF). Cancer cells frequently accumulate mutant p53 and a subset of these cancer cells become addicted to it for their survival. While mutant p53 is inherently labile, as is wild type p53, in cancer cells mutant p53 becomes constitutively stable. In part, this is due to the interrupted auto-regulatory loop with Mdm2. However, Mdm2 alone cannot explain the stability of mutant p53 in many cancer contexts. We therefore argued that additional factors are responsible for its stability in cancer cells. In order to identify the major players in the regulation of mutant p53, we performed a high-throughput RNAi screen through which we evaluated 18,120 genes for their effects on mutant p53 levels in two different mutant p53 expressing cell lines. Based on network analyses, pathway analyses and extensive knowledge mining, we selected 37 candidate genes to be validated through p53 immunoblotting. Out of 37 genes, we chose to investigate a potential regulator of mutant p53, which will be referred to as candidate one (C1). We observed that C1 interacts with mutant p53 and is capable of regulating mutant p53 protein expression but not mRNA expression. Moreover, we observed reduced mutant p53 ubiquitination in C1 knockout mouse embryonic fibroblasts. Our results highlight a previously unknown mode of mutant p53 regulation in cancer cells, thus opening up opportunities for targeting aggressive cancers with mutant p53. Future studies aim to explore the functional consequences of C1-mutant p53 interaction on oncogenic functions of mutant p53.