Objective To investigate the role of p53 gene in neurobehavior activities and effects on the number of neurons of barrel cortex in mice. Methods A total of 45 8 ~ 12 weeks old p53 knockout ( KO) mice with C57BL/ 6 background and 38 wild-type (WT) mice of the same age and background were included as the experimental group and the control group, respectively. The open-field test, Y-maze test and texture discrimination task were used to evaluate anxiety- like behavior, locomotor activity, working memory and whisker sensitivity in mice. Nissl staining was used to observe changes in neuronal numbers in layer II/ III of barrel cortex. Results Compared with WT mice, p53 KO mice did not show any significant difference in the time spent in the center (P> 0. 05) or total distance moved (P> 0. 05) of the open field apparatus, the percentage of spontaneous alternations (P> 0. 05), and the numbers of arms entries (P> 0. 05) in the Y-maze test. However, the percentage of time exploring objects with novel texture was significantly decreased (P< 0. 01). The number of neurons in layer II/ III of barrel cortex of p53 KO mice was significantly reduced compared with that of WT mice (P< 0. 01). Conclusions Deletion of p53 gene did not lead to anxiety-like behavior in mice. Moreover, locomotor activity and working memory were not affected by p53 deletion. However, p53 deletion impacted the ability to discriminate novel textures, that is, whisker sensitivity, which may be related to the decreased number of neurons in layer II/ III of the barrel cortex.