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Low rectal cancer is a subtype of colorectal cancer at a special anatomic site with distinct biological behavior. TP53 is one of the most important cancer suppressor genes, and its structural variation and abnormal expression has been revealed to be associated with multiple cancer types. However, to the best of our knowledge, the association of p53 protein expression with its gene polymorphism, biological behavior and prognosis in low rectal cancer has not been clarified. Therefore, the current study aimed to explore these associations. In the present study, 347 patients with low rectal cancer and 353 controls were enrolled. Kompetitive Allele-Specific Polymerase Chain Reaction was used to detect five polymorphic sites of the TP53 gene (rs1042522, rs12947788, rs1625895, rs2909430 and rs12951053), while immunohistochemistry was used to detect the protein expression of TP53. The associations between p53 protein expression and TP53 polymorphism, biological behavior and prognosis in low rectal cancer were systematically analyzed. In low rectal cancer, p53 protein expression was markedly higher in TP53 rs1042522 mutant carriers compared with that in other genotypes where expression was higher in poorly differentiated, III–IV phase and T3-4 phase tumors, and in III–IV phase female patients. The survival time of patients with low p53 protein expression was evidently longer in females, non-smokers and patients >60 years old. In summary, p53 protein expression was identified to be affected by TP53 rs1042522 polymorphism, and was associated with the biological behavior and prognosis of low rectal cancer. TP53 rs1042522 and the associated protein expression could be used as indicators for biological behavior and prognosis in low rectal cancer. [ABSTRACT FROM AUTHOR]