Speaking up for patient safety among health care professionals is important because it can contribute to the prevention of adverse patient events, such as medication errors, infections, wrong-site surgical procedures, and other sentinel events. This systematic review identified factors that facilitate or inhibit nurses’ willingness to speak up regarding patient safety in East Asian hospitals. Following the steps of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, four databases, including PubMed, CINAHL, PsycInfo, and Web of Science, were searched. Nine studies were analyzed in this review, including five qualitative and four quantitative studies published between 2014 and 2019. Quality of included studies were evaluated using the Mixed-Method Appraisal Tool. Data synthesis was based upon qualitative-led synthesis adopting two existing multilevel frameworks on safety voice and employee voice signals. Four studies were conducted in Japan, three in South Korea, one in Hong Kong, and one in Taiwan. We organized factors influencing East Asian nurses’ willingness to speak up regarding patient safety according to the following four contexts: individual (motivation toward patient safety, organizational commitment, perceived effectiveness and importance of speaking up, and assertive personality), team (positive relationship and team trust, team culture, and mentoring), organizational (hospital administrative support and organizational culture) and sociocultural (hierarchy and power differential and collectivistic culture). However, due to the limited number of studies conducted in East Asian hospitals, further studies with larger cohort samples of nurses in various East Asian countries should be conducted to deepen our understanding of nurses’ willingness to voice their concerns for patient safety.