Gestational trophoblastic neoplasia (GTN) refers to malignant diseases originating from placental trophoblast cells. Despite high complete remission rates with standard treatments, the adverse effects of chemotherapy, variation in treatment regimens, and the psychological impact on patients significantly influence the prognosis. This study aims to identify factors influencing the time to serum human chorionic gonadotropin (hCG) negativization, thereby contributing to the optimization of patient management strategies. We conducted a retrospective analysis of 206 patients diagnosed with invasive mole and gestational choriocarcinoma treated at the First Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to May 2022. Patients- and treatment-related risk factors were collected. We evaluated 33 variables potentially related to the duration of serum hCG negativization with statistically significant variables from univariate analyses subsequently included in multivariate Cox regression analysis. Through univariate analysis, we identified 11 significant predictors that related with hCG negativization, including body mass index (BMI), age at menarche, number of miscarriages, prior pregnancy status, time since prior pregnancy, maximum tumor diameter, maximum lung tumor diameter, alkaline phosphatase levels, pre-chemotherapy hCG levels, initial chemotherapy regimen, and whether hysterectomy was performed. Cox regression analysis highlighted that increased BMI was associated with a shorter time to hCG negativization (HR=1.730, P=0.001). In contrast, higher pre-treatment hCG levels, longer time since the last pregnancy, and undergoing hysterectomy were associated with prolonged hCG conversion times. In conclusion, this study underscores the importance of individual factors such as BMI, pre-treatment hCG levels, and surgical interventions in determining the duration of hCG negativization in GTN patients. These findings suggest that tailored treatment strategies considering these factors could enhance treatment efficacy and patient outcomes. Increased awareness and careful consideration of these factors should be integral to pre-treatment planning and patient counseling.