Herein, we aimed to unveil the diagnostic value of serum NLRP3, MMP‐9 and IFN‐γ levels in the diagnosis of intracranial infections and hydrocephalus in patients with severe craniocerebral trauma after craniotomy, and our findings highlighted that serum MMP‐9, NLRP3 and IFN‐γ levels were linked to the risk of hydrocephalus and intracranial infections after craniotomy in patients with severe craniocerebral trauma. Here, MMP9 is linked to Hydrocephalus.