To analyze the clinical effect of minimally invasive hematoma removal combined with monostearic ganglioside treatment for hypertensive cerebral hemorrhage. Methods: We selected 121 patients with hypertensive cerebral hemorrhage for prospective study and randomly divided them into the single-pass minimally invasive group (61 cases) and combined treatment group (60 cases). Patients in the single-pass minimally invasive group were treated with minimally invasive hematoma removal while patients in the combined treatment group were treated with minimally invasive hematoma removal combined with monostearic ganglioside. Fourteen days after treatment, the pre- and post-surgery inflammatory factor indicators including the procalcitonin (PCT), interleukin-6 (IL-6), IL-1 β, and C-reactive protein (CRP) were compared between the two groups; the amino acid neurotransmitter indicators γ-aminobutyric acid (GABA) and glutamic acid (Glu), peptide neurotransmitter indicators neuropeptide Y (NPY) and substans P (SP), and nerve injury indicators S100B protein, myelin basic protein (MBP), neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP) were also compared. The extent of nerve function defect in both groups was assessed and compared 4 months after treatment. Results: Compared with before treatment, the levels of PCT, IL-6, IL-1β, CRP, Glu, NPY, SP, S100B protein, MBP, NSE, and GFAP in both groups 14 days after treatment were significantly lower (P<0.05), and the decrease in the combined treatment group was more significant than that in the single-pass minimally invasive group (P<0.05). GABA levels were increased in both groups, and the increase in the combined treatment group was more significant (P<0.05). Compared with before treatment, the neurological impairment of both groups 4 months after treatment was significantly reduced (P<0.05), and the neurological impairment of the combined treatment group was lower than that of the single-pass minimally invasive group (P<0.05). Conclusion: Minimally invasive hematoma removal combined with sialic acid ganglioside can significantly improve the inflammatory factor levels and neurotransmitter indicators and lessen the damage to nerve function in hypertensive cerebral hemorrhage patients. The combined treatment is superior to using minimally invasive surgery alone.