Background & Objective: Educational simulators have been proposed as effective tools for enhancing learning and improving students' skills when preparing for the workplace. This study aimed to determine the effect of simulation-based training in a hospital information system on nursing students' informatics skills before their internship. Materials & Methods: This quasi-experimental study was conducted in the first semester of the academic year (2023-2024) with 26 third-semester undergraduate nursing students at the Ferdows Faculty of Medical Sciences. The students were randomly divided into control and intervention groups. The educational content featured a simulation of the inpatient module of a hospital information system. Students in the intervention group were given access to this module's developed training and practice sections over two weeks. After one month, the test section for this module was made available to both the intervention and control groups. Data analysis was conducted using SPSS version 26, where descriptive statistics were calculated, and the Mann-Whitney test was utilized. Results: After the test, the mean scores of students in the intervention and control groups were 35.69 ± 3.9 and 29.85 ± 5.01 (out of 41), respectively. The difference between the mean scores of the two groups was significant (p = 0.003, Effect size = 0.59). Furthermore, there was no significant correlation between sex, age, or grade point average and the mean test scores in either group (P > 0.05). Conclusion: Simulation-based training can potentially enhance nursing students' skills in utilizing hospital information systems. Considering the emphasis on the role of health information systems in the management of healthcare settings, it is recommended that simulated HIS training be included in the educational curriculum of nursing students.