The present study aimed to investigate whether the neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage (SAH). In a mouse model of SAH, microRNA‑22 expression was upregulated. In addition, downregulation of microRNA‑22 in HEB cells increased the mRNA expression levels of interleukin (IL)‑6, induced cysteine rich angiogenic inducer 61 (Cyr61) expression, and suppressed the protein expression levels of B‑cell lymphoma 2‑associated X protein (Bax) and caspase‑3 activity. Treatment with the p53 inhibitor, pifithrin‑α, suppressed p53 protein expression, increased IL‑6 mRNA expression, decreased microRNA‑22 expression, Bax protein expression and caspase‑3 activity, and induced Cyr61 expression in mice with SAH. Furthermore, p53 expression was knocked down using p53 small interfering RNA, which suppressed microRNA‑22 expression and increased IL‑6 mRNA expression, inhibited Bax protein expression and caspase‑3 activity, and induced Cyr61 expression in HEB cells. The present study demonstrated that the neuroprotective effects of p53/microRNA‑22 may regulate inflammation and apoptosis in SAH. Reverse transcription quantitative polymerase chain reaction (qPCR) was used to analyze the expression of microRNA-22, western blot analysis was used to analyze the protein expression of Bax and Cyr61.