〔Abstract〕 Objective To observe the curative effect of Urinary Kallidinogenase combined with Butylphthalide in the treatment of severe acute cerebral infarction, and to explore its effect on improving serum factors in patients. Methods A total of 85 patients with severe acute cerebral infarction admitted to Jiamusi Central Hospital from October 2019 to May 2021 were selected and divided into a control group (42 patients received Butylphthalide) and an observation group (43 patients received Butylphthalide + Urinary Kallidinogenase) by random number table method. Both groups were treated for 4 weeks.The scores of the mini-mental state examination (MMSE), the National Institutes of Health stroke scale (NIHSS), the levels of serum factors and the survival of the two groups were compared before and after treatment. Results After treatment, MMSE score of the observation group was higher than that of the control group, NIHSS score was lower than that of the control group, and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypersensitive C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9) of the observation group were lower than those of the control group. The levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) were higher than those of the control group. The survival rate and mortality of the observation group were higher than those of the control group, and the differences were statistically significant (P < 0.05). Conclusion Butylphthalide combined with Urinary Kallidinogenase in the treatment of severe acute cerebral infarction can improve the neurological function of patients and correct the level of related serum factors, and the clinical effect is good.