Abstract Background: Post-transplant lymphoproliferative disorder (PTLD) is a dangerous complication of liver transplantation. This study aimed to analyze the risk factors associated with PTLD after liver transplantation in children. Method: We retrospectively analyzed collected clinical and laboratory data of patients treated and followed-up at Shanghai Children’s Medical Center between January 2012 and January 2019. Twenty-four patients with PTLD were enrolled in this study using a 1:2 pairing design. Each case was matched with two controls who had undergone liver transplantation within the same year and did not develop PTLD during the follow-up period. In total, 72 patients were included in this study. Result: No differences in age, gender, weight, primary disease, or type of liver transplantation were observed between those with and without PTLD. Graft weight, graft body weight ratio, transplant type, intraoperative blood loss, blood type, and CMV/EBV infection status of donors and recipients were not related to the occurrence of PTLD. Univariate analysis demonstrated statistically significant differences in EBV infection, tacrolimus blood concentration, PTL, AST, ALT, and CHOL between those with and without PTLD. Multivariate logistics regression analysis demonstrated that EBV infection was an independent risk factor for PTLD. A close relationship was observed between EBV-DNA peak time after transplantation and PTLD onset time. Additionally, the higher the tacrolimus blood concentration, the more difficult it was to control EBV infection. Conclusion: EBV infection is an independent risk factor for PTLD. When uncontrolled proliferation of EBV occurs after organ transplantation, the dosage of immunosuppressive agents should be appropriately reduced