Objective To investigate the expression of mutant p53 in skull base chordoma and its association with patients’ prognosis and clinical features， and to verify the function of mutant p53 in skull base chordoma at the cellular level.Methods A total of 49 patients with skull base chordoma who underwent surgical treatment in Beijing Tiantan Hospital， Capital Medical University， from January 2005 to December 2014 were enrolled， and paraffin sections were used for immunohistochemical staining to analyze the association of the expression of mutant p53 with the prognosis and clinical features of the patients with skull base chordoma. The p53 gene in the skull base chordoma cell line UCH-1 was knocked down by siRNA to analyze the change in cell function before and after knockdown.Results At the protein level， the expression level of mutant p53 （odds ratio = 1.040， 95% confidence interval： 1.007~1.073， P = 0.016） was a risk factor for tumor progression after surgery； in addition， the expression of mutant p53 in bone-infiltrating tumors was significantly higher than that in non-infiltrating tumors （t = 3.319， P = 0.002）， the expression of mutant p53 in hard tumors was significantly higher than that in soft tumors （t = -3.503， P = 0.001）， and the expression of mutant p53 in tumors with rich blood supply was significantly higher than that in tumors without rich blood supply （t = 2.081， P = 0.043）. At the cellular level， there was a significant difference in cell viability between the control group and the p53 knockdown group at different time points （F = 305.715， P = 0.000）， and the p53 knockdown group had a significantly lower cell apoptosis rate than the control group （t = -3.961， P = 0.017）. Compared with the control group， the p53 knockdown group had a significant increase in the number of tumor cells penetrating into the lower compartment at 6 hours （t = -5.232， P = 0.014）， 12 hours （t = 4.778， P = 0.017）， and 24 hours （t = -9.303， P = 0.003）.Conclusions The increased expression of mutant p53 in skull base chordoma may increase the risk of tumor progression after surgery， and the expression of mutant p53 is associated with tumor texture， invasion， and blood supply. There are increases in the proliferation and invasion abilities of chordoma cells and a reduction in apoptosis after the expression of p53 is inhibited.