The high rate of postencephalitic epilepsy (PE) contributes to the unfavorable clinical outcome of herpes simplex virus-1 encephalitis (HSE). We aimed to identify the risk factors and explore possible mechanisms of PE in childhood following HSE. We conducted a retrospective review of children diagnosed with HSE and patients were categorized into two groups based on the presence or absence of PE. Multivariate logistic regression analysis was used to analyze factors associated with PE. Furthermore, cytokine and albumin levels in paired cerebrospinal fluid (CSF) and blood samples during acute HSE were also retrospectively reviewed. 97 HSE patients were included in the study and PE was diagnosed in 46. On multivariate analysis, the features predictive of PE (presented as odds ratio [OR] with confidence intervals [CIs]) were status epilepticus (OR 9.38, CI 1.71-10.37), focal seizures (7.41, 1.42-16.97), and restricted diffusion on MRI (6.15, 1.16-20.31). The median QAlb value (CSF to serum albumin ratio, a marker of blood-brain-barrier [BBB] integrity), levels of interleukin (IL)-6 and IL-6:IL-10 ratio in CSF were higher in children with PE during acute HSE. However, CSF levels of IL-10 were higher in non-PE patients. Furthermore, greater CSF IL-6 levels were associated with higher QAlb. These results demonstrated that enhanced BBB impairment and exaggerated proinflammatory response may play a role in the pathogenesis of PE following HSE.