Objective: To evaluate the effect of hyoscine on pain and tenderness, rebound tenderness and appendicitis patients before surgery and this study can be considered as the first study investigated the efficacy of hyoscine on pain, tenderness, and rebound tenderness in patients with appendicitis.Methods: In this single-group, prospective interventional study (before-after) according to inclusion and exclusion criteria, 70 patients with pain in the right lower abdomen and typical symptoms of appendicitis were evaluated and after surgery, diagnostic accuracy was examined by pathologic results. The pain was evaluated before and after administration of hyoscine by numerical and verbal examination. Tenderness and rebound tenderness were also determined.Results: The mean age of patients was 26.81±7.66. Totally, 42 patients (60%) had reduction in pain, 50 patients (71% percent) had reduction in tenderness, and 39 (55%) had reduction in rebound tenderness after treatment with the drug. A statistically significant reduction of pain and tenderness, rebound tenderness was observed in all of men after administration of hyoscine (p<0.001) but in women, the reduction of severity of tender results was only significant (p=0.002). Data analysis in women and men together showed the significant reduction of pain, tenderness, and rebound tenderness (p<0.001).Conclusion: According to the results, hyoscine can reduce pain, tenderness, and rebound tenderness. So, it seems that hyoscine is a good candidate for patients with appendicitis.IRCT registration number: IRCT2015111825123N1