Objectives: Mushroom intoxication with Amanita phalloides has a high incidence throughout the world. Treatment for this intoxication is similar in different centers, but N-acetylcysteine is rarely used. In this study, we aimed to investigate the effects of N-acetylcysteine treatment in patients with Amanita phalloides intoxication.Methods: A total of 40 patients with Amanita phalloides intoxication were included in this retrospective study. The study group consisted of 24 patients who were administered N-acetylcysteine in addition to the standard regimen; the control group consisted of 16 patients who were treated only with the standard treatment. Treatment results and biochemical measurements of groups were compared.Results: According to the biochemical measurements, it was found that patients in the control group were affected more seriously by Amanita phalloides than those in the study group. The mortality rate was lower in the study group (4.4% vs. 18.7% in the control group).Conclusions: Amanita phalloides intoxication can be successfully treated with N-acetylcysteine in addition to the standard regimen. Significantly, the simplicity of administration, good tolerance, and an affordable cost make N-acetylcysteine a viable option for the treatment of Amanita phalloides intoxication. The low mortality rate presented in the study group may be ascribed to N-acetylcysteine administration.