Objective: To compare the efficacy of 3% hypertonic saline(HTS) and 10% HTS combining with 20% mannitol(MT) in the treatment of high cranial pressure after acute massive cerebral infarction. Methods: A total of 40 patients with acute massive cerebral infarction complicated with intracranial hypertension diagnosed and treated by the inpatient Department of Encephalopathy, Guilin Hospital of Traditional Chinese Medicine from 2020 to 2023 were selected in this study. Selected patients were divided into two groups(20 patients in each group) according to random number table method. The treatment group(groupA) was treated with 10% HTS 60 mL and 20% MT 125 mL at alternate static points for cranial pressure reduction(the specific frequency was referred to the adjustment of intracranial pressure), and the control group(groupB) was treated with 130 mL of 3% HTS and 125 mL of 20% MT sequentially. Intracranial pressure(ICP), mean arterial pressure(MAP) and central venous pressure(CVP) were continuously monitored before and after medication in both groups, and the corresponding cerebral perfusion pressure(CPP) was calculated according to ICP and MAP. The duration of effective reduction of intracranial pressure, the maximum reduction and duration of intracranial pressure in enrolled patients were recorded, and the blood sodium value and plasma osmotic pressure were recorded before, 2 and 6 hours after medication. Results: A total of 40 cases were enrolled, with 36 cases completed and 4 cases rejected. The statistical results showed that ICP, MAP, CPP, blood sodium and osmotic pressure were significantly different between the two groups before and after treatment in different periods(P＜0.05). After 2 and 6 h of medication, ICP in groupA was lower than that in groupB(P＜0.05), while MAP, CVP, CPP, sodium and plasma osmotic pressure were higher than those in the control group(P＜0.05). ICP was the most significantly decreased 2 h after treatment(P＜0.05), and ICP was the most significantly decreased in the range of 150 to 160 mmol/L of blood sodium(P＜0.05). Conclusion: 3% and 10% HTS can effectively reduce ICP in patients with acute large area cerebral infarction, but 10% HTS has more lasting effect on reducing intracranial pressure and less influence on blood sodium and internal environment, which is worthy of clinical promotion.