Objectives: To investigate the clinical effect of mild hypothermia combined with intravenous thrombolysis in the treatment of acute cerebral infarction. Methods: Eighty-eight patients with acute cerebral infarction in Binzhou People’s Hospital between May 2018 and August 2019 were randomly selected and divided into a control group and an observation group according to the random number table method, with 44 patients in each group. The control group was given intravenous thrombolysis; the observation group was treated with mild hypothermia (30-350C) in addition to intravenous thrombolytic thrombolysis. The clinical efficacy, incidence of complications, oxidative stress indexes, inflammatory factor level, neurological function, and mental state of the two groups before and after treatment were compared. Results: The clinical efficacy of the observation group was significantly better than that of the control group, and the difference was statistically significant (P<0.05). There was no significant difference in the levels of oxidative stress indexes and inflammatory factors between the two groups before treatment (P<0.05). After treatment, the levels of oxidative stress indexes and inflammatory factors of the two groups significantly improved, and the improvement of the observation group was better than that of the control group; the differences were statistically significant (P<0.05). There was no significant difference in the neurological function and mental state between the two groups before treatment (P<0.05). After treatment, the neurological function and mental state of the two groups significantly improved, and the improvement of the observation group was better than that of the control group; the differences were statistically significant (P<0.05). There was no significant difference in the incidence of complications and mortality between the two groups (P>0.05). Conclusion: Thrombolytic therapy combined with mild hypothermia has a good efficacy in the treatment of acute cerebral infarction. The therapy can improve the neurological function of patients with acute cerebral infarction by significantly improving the oxidative stress index and relieving the inflammatory reaction. Its efficacy is better than single thrombolytic therapy. doi: https://doi.org/10.12669/pjms.37.7.4499 How to cite this:Zhang S, Gao L, Wo X, Wang Z. Clinical observation of mild hypothermia combined with intravenous thrombolysis in treating patients with acute cerebral infarction. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4499 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.