Abstract: Objective：To investigate the clinical effect of combined shortrange high dosage Anisodamine with Dexamethasone in the treatment of severe multiple trauma patients and to state the mechanism. Methods：Totally 70 patients with severe multiple trauma were selected and divided into study group and control group according to random number table method. The research group was treated with Anisodamine combined with Dexamethasone, and the control group was given potassium magnesium aspartate combined with Dexamethasone. The clinical efficacy of the two groups was observed, and the levels of tumor necrosis factor (TNF) and lipid hydroperoxide (LPO) were compared between the two groups before and after treatment. In addition, the changes of liver and kidney function in the two groups were observed before and after treatment. Results：The fatality rate of the study group was 11.43%, and the control group was 22.86%, and the difference was statistically significant (P＜0.05). After treatment, the TNF, LPO levels were (77.02±12.77) mol/L and (2.94±0.72) mol/L respectively in study group while （112.46±15.91） μmol/L and （5.03±1.03） μmol/L respectively in control group, and the differences were statistically significant (P＜0.05). Before and after treatment, there was no significant difference in the levels of liver and kidney function between the two groups, and the difference was not statistically significant (P＞0.05). Conclusions：The combined shortrange high dosage Anisodamine with Dexamethasone can significantly reduce the fatality rate of severe multiple trauma patients with safe and reliable application and its mechanism is likely to inhibit the level of LPO and TNF.