So, we evaluated cognitive function of mice after IH treatment by MWM test, which demonstrated that SENP1 depletion seriously aggravated IH‐induced cognition decline with the evidence of increased escape latency, decreased percentage of time spent in the target quadrant and the frequency of passing through the target platform area in mice with SENP1 knockdown after IH treatment, which suggested that SENP1 plays essential roles in anti‐inflammation and protective effect in IH‐induced cognitive impairment. Here, SENP1 is linked to isolated hemihyperplasia.