Post-hemorrhagic hydrocephalus (PHH) necessitates surgical intervention to alleviate symptoms and prevent neurological sequelae. The role of inflammatory cytokines in PHH pathophysiology remains unclear, prompting the need for a comprehensive investigation of their cerebrospinal fluid (CSF) profile. This study aimed to investigate the characteristics of patients with PHH undergoing shunt surgery and evaluate CSF cytokine levels in these patients. We conducted a prospective, multi-center trial to determine the inflammatory cytokine levels and evaluate shunt outcomes in PHH patients during the period from December 2019 to June 2021. Upon identification of candidates for shunt surgery, CSF samples were obtained and stored for subsequent analysis of inflammatory cytokines. Outcome measures included the symptomatic control rate (SCR), shunt failure rate, Evans index, and modified Rankin Scale (mRS) score at 6 months postoperatively. SCR assessed via Kiefer Hydrocephalus Scale (KHS: gait, cognition, incontinence, headache, dizziness). 24 patients were included in the study. CSF cytokine levels were compared between PHH patients and two control groups. The results showed elevated CSF tumor necrosis factor-α (TNF-α) level in PHH patients compared to controls, indicating potential inflammatory response in these patients. However, no significant differences were observed in other cytokines, including interleukin-1α (IL-1α), IL-1β, IL-6, and IL-10. Furthermore, shunting outcomes were evaluated, demonstrating improvements in ventricular parameters and neurofunctional outcomes postoperatively. Although shunt failure occurred in 16.7% of cases, the majority of patients experienced satisfactory outcomes with decreased morbidity and improved quality of life. No severe adverse events were reported during the 6-month follow-up period. There were no statistically significant differences in cytokine levels between the shunt-success and shunt-failure groups for TNF-α, IL-1α, IL-1β, IL-6, and IL-10. This study provides insights into the clinical characteristics, inflammatory profiles, and shunting outcomes of PHH patients, highlighting the potential role of TNF-α in the pathophysiology of PHH. Further research is warranted to elucidate the underlying mechanisms and optimize treatment strategies for this patient population.