The coronavirus disease (COVID-19) broke out in China in January 2020 and has been effectively controlled in April 2020 after China’s relentless efforts. People’s engagement in disease-related preventive behaviors is crucial in containing such infectious disease. Vulnerable populations often have higher chances of developing severe illness from COVID-19 and the mortality rate is also higher. Thus, at-risk populations for COVID-19 request extra attention. The current study conducted a national online survey among vulnerable populations in China in early February 2020 to examine their engagement in coronavirus-related preventive health behaviors (e.g., frequent handwashing) and the potential determinants including factors from the Health Belief Model, trust in different media sources, and health literacy. The results suggested that the vulnerable populations’ engagement in coronavirus-related preventive behaviors were significantly associated with barriers, benefits, self-efficacy, trust in doctors’ social media, and trust in TV for COVID-19-related information. Besides, barriers, benefits, self-efficacy, trust in doctors’ social media, and trust in TV mediated the effects of health literacy on preventive behaviors. Our findings provided directions for future health promotions and interventions targeting vulnerable populations to enhance their preventive behaviors in China.