A high quality of life (QoL), an individual’s subjective assessment of overall life condition, has been shown to have a protective effect against negative behaviors. However, whether QoL protects people from the harmful impact of health rumors is still unknown. In this study, a national survey in China (n = 3633) was conducted to explore the relationship between health rumor belief (HRB) and QoL, which includes physical, psychological, social, and environmental domains. The results show that people with a poor perception of their physical health are more likely to believe health rumors. Additionally, those who had better self-reported satisfaction in social relationships were more susceptible to health rumors. Furthermore, women and older adults showed a greater belief in health rumors. This study expands upon our understanding of how people with different QoL levels interact with false health-related information. Based on health-rumor-susceptible groups, several essential online and offline strategies to govern health rumors are also proposed.