The COVID-19 pandemic has sparked hostility against Chinese immigrants and sojourners in the U.S. and other countries. Making the situation worse, strong resentment against this group has also emerged in China due to the fear of returnees spreading the disease. Integrating research on acculturation and hostile media perception, we examined how such bilateral hostility along with different acculturation components (i.e., cultural identification, COVID-19-related media use, and individualistic-collectivistic value) influenced U.S.-dwelling Chinese’s psychological well-being during the COVID-19 pandemic. Based on the results from a two-wave survey assessing the cultural identity and value, COVID-19-related media use, and psychological distress of a group of relatively young and highly educated U.S.-dwelling Chinese (N = 1,256) between March and April 2020, we found that identification with both U.S. and Chinese cultures alleviated immigrants and sojourners’ psychological distress. Further, COVID-19-related media use served as a stressor during the pandemic, and perceived hostility from China led to stronger psychological distress among U.S.-dwelling Chinese.