Background and objective Appendicitis resection is one of the most common surgical procedures. Hospitalization expenses are a major determinant of appendicitis treatment. This study explored the factors influencing hospitalization expenses of appendicitis patients in Anhui province and provided a scientific basis for reasonably controlling medical expenses. Methods A multi-stage random cluster sampling method was used to collect case information on 2,164 patients who underwent appendicitis surgery at 6 county-level public hospitals in Anhui province, China. Path analysis was used to study the factors influencing hospitalization expenses of appendicitis patients. Results The average length of stay was 5.62 ± 2.64 days, with a median of 5 days; the average hospitalization expenses were 6,109.60 ± 2,109.44 CNY, with a median of 5,511.93 CNY. The direct effect of length of stay was 0.535. Surgical grades, surgical methods, and chronic appendicitis directly affected hospitalization expenses, with direct effects of 0.149, 0.081, and -0.037; surgical costs, anesthesia costs, disease outcomes, age, acute simple appendicitis, and operative duration not only directly affected hospitalization expenses, but also indirectly affected hospitalization expenses, the total effects were 0.283, 0.045, 0.200, 0.202, -0.162, and 0.062, respectively. The total number of surgeons and assistants only indirectly affected hospitalization expenses, with indirect effect of 0.020. Conclusions The length of stay is the most important factor affecting hospitalization expenses. Based on controlling the average length of stay, combined with shortening operative duration, conducting health education, strengthening controllable factors, and other comprehensive measures can effectively reduce the economic burden of patients and hospitals.