Objective: To explore the effect of anxiety, depression and hypertension on quality of life (QOL) of patients with gynecological tumor and the interaction among them, and the moderating effect of social support. Design: Cross-sectional design Setting: December 2019 to July 2020, the COVID-19 outbreak phase. Population or Sample: A total of 695 gynecological cancer patients were collected. Methods: The study used the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Functional Assessment of Cancer Therapy Genera tool (FACT-G), and the Multidimensional Scale of Perceived Social Support Scale (MSPSS). Regression analysis and the simple slope analysis were conducted. Results: QOL of patients with anxiety and hypertension had seriously deteriorated [OR=10.297, 95%CI (5.647-18.775)]. And QOL of patients with depression and hypertension also had seriously deteriorated [OR=11.846, 95%CI (6.597-21.271)]. Calculated by crossover analysis, the synergy index, attributable proportion and relative excess risk due to interact of anxiety and hypertension were1.698,0.371 and 3.822, and the correlation index of interaction between depression and hypertension were 1.475, 0.295, and 3.493. The Social Support &Depression interaction term and Social Support &Anxiety interaction term were negatively correlated with QOL (p<0.01), and explained an extra 5.7% and 5.6% of the variance respectively (p<0.01). Conclusion: Anxiety, depression and hypertension have interaction on the QOL of patients with gynecological tumors. Social support can significantly moderate the relationship between depression, anxiety and QOL respectively. Funding: National Key R&D Program of China (Grant #2018YFC1311600). Keywords: quality of life, depression, anxiety, social support, hypertension, moderating effect