Objective To explore the risk factors of acute non-simple appendicitis in children, and to establish a prediction model. Methods Retrospective analysis was performed with the clinical data of 582 children with acute appendicitis who underwent laparoscopic appendectomy and were diagnosed by pathology in our hospital from Jan. 2018 to Dec. 2019. According to the intraoperative findings and pathological types, the patients were divided into non-simple appendicitis group (382 cases, including suppurative, gangrene and perforation) and simple appendicitis group (200 cases). The clinical data of the 2 groups were compared and statistically significant variables were used for multivariate logistic regression analysis to identify risk factors of acute non-simple appendicitis, and finally to establish a logistic regression prediction model. The performance of the prediction model was assessed by receiver operating characteristic (ROC) curve. Prospective validation of the prediction model was conducted with 160 patients with acute appendicitis undergoing appendectomy in our hospital from Jan. to Dec. 2020. Results Of the 582 patients, 382 (65.6%) had non-simple appendicitis. Multivariate logistic regression analysis demonstrated that white blood cell (WBC) (odds ratio［OR］＝1.305, 95% confidence interval［CI］1.189-1.432, P＜0.001), neutrophil percentage (NP) (OR＝1.046, 95% CI 1.012-1.080, P＝0.007), C reactive protein (CRP) (OR＝1.046, 95% CI 1.010-1.082, P＝0.011), and albumin (ALB) (OR＝0.973, 95% CI 0.952-0.995, P＝0.014) were independent risk factors for non-simple appendicitis in children. The logistic regression equation based on the 4 factors was logit(P)＝ —5.614＋0.263×WBC＋0.045×NP＋0.045×CRP—0.027×ALB. The probability model was P＝1/(1＋Exp［—5.614＋0.263×WBC＋0.045×NP＋0.045×CRP—0.027×ALB］). The Hosmer-Lemeshow test indicates that this model has high fitting degree (P＝0.622). The area under curve of the ROC curve for the prediction model was 0.931 (95% CI 0.896-0.957, P＜0.001), with a sensitivity of 0.830 and a specificity of 0.905. Prospective validation showed that the sensitivity and specificity of the prediction model were 0.882 and 0.820, respectively. Conclusion Increased white blood cell count, neutrophil percentage and CRP level, and hypoalbuminemia are independent risk factors for acute non-simple appendicitis in children. The prediction model based on the above factors has good diagnostic value and can help differentiate between acute simple and non-simple appendicitis.