Aims Frailty is closely related to the prognosis and quality of life of patients with heart failure (HF). However, the predictors of it are still unclear. Our study aimed to describe the frailty status of Chinese hospitalized patients with heart failure and explore predictive factors guided by Theory of Unpleasant Symptoms. Methods and results In this cross-sectional descriptive study, questionnaire-based survey was conducted among 323 patients hospitalized with heart failure in three tertiary hospitals in Wuhan, China. Frailty was measured by the Tilburg Frailty Indicator (TFI) in this study. The model based on Theory of Unpleasant Symptoms fits the sample well (root mean square error of approximation = 0.063, goodness of fit index = 0.977, normed fit index = 0.901, comparative fit index = 0.940). Frailty among Chinese patients hospitalized with heart failure was at high level (TFI = 6.57 ± 3.05). General demographic characteristics (older age, female gender, lower education level, and medical payment method), physical factors (higher New York Heart Association cardiac function class), psychological factors (more severe depression), and social factors (poorer social support) were significant predictors of more severe frailty (p < 0.05). Depression played an important mediating role in this study. Conclusions Theory of Unpleasant Symptoms can be used to guide the research on the frailty of heart failure patients. It is suggested to strengthen emotional support and health education for heart failure patients in China. In addition, more attention should be paid to the less educated population by providing more personalized health guidance.