Cancer is the second cause of human death worldwide. p53 function is lost in over 50% of human cancers evidencing the role of p53 in tumorigenesis. The majority of the p53 mutations are clustered in the protein DNA-binding domain, particularly within regions so-called hot spots. Mutations in the R248 residue are the most common in breast, colon, head-neck, lymphoma/leukemia and skin cancers. p53 is a transcriptional factor with flexibility for DNA binding, allowing the generation of alternate conformations. It is known that, at pH 5.5, wild-type p53 acquires a ”molten globule" state (MG), which is characterized by loss of tertiary structure, exposition of hydrophobic domains and secondary structure increase. We investigated if the p53 point mutant R248Q would also adopt a molten globule fold. We have incubated R248Q at different pHs to isolate the MG state and investigate its structural properties by spectroscopic techniques in order to compare with the results at physiological pH (7.2). At low pHs, the fluorescence data demonstrate a greater exposition of aromatic residues, what is expected for a molten globule-like fold. Far-UV circular dichroism measurements show that the protein has a substantial amount of secondary structure in pH range of 4.5 to 5.5. Moreover, the binding of R248Q to the compound 8-anilino-2-naphthyl sulfonic acid indicate exposure of hydrophobic regions at the same pH range. We have then decided to work at pH 5.0 and compared with the results at pH 7.2. Our data show that the effect of high pressure on the R248Q MG state is fully reversible and does not lead to aggregation of the protein, in contrast with what was observed at pH 7.2. In addition, we observed that the R248Q at both pHs presents different unfolding profiles when treated with chemical denaturants. Curiously, experiments at high temperatures allowed the recovery of the secondary structure but not of the tertiary one. Concluding, our results indicate that R248Q displays distinct folding characteristics at pH 5.0 and 7.2. Studies on flexibility and alternate conformations of p53 may help to explain the factors that govern the rate and mechanism of protein folding, being a prerequisite for the discovery of new therapies involving p53.