Despite the importance of speaking up for patient safety, hesitancy to do so remains a major contributing factor to communication failure. This study aimed to investigate the experiences of South Korean nurses in speaking up to prevent patient safety incidents. Twelve nurses responsible for patient safety tasks or with experience in patient safety education were recruited from five hospitals (three university hospitals, two general hospitals) in city “B”. Data were collected through open-ended questions and in-depth interviews, transcribed, and analyzed using the inductive content analysis method. The study resulted in the identification of four main categories and nine subcategories that captured commonalities among the experience of the 12 nurses. The four main categories were as follows: the current scenario of speaking up, barriers to speaking up, strategies for speaking, and confidence training. There is a scarcity of research on speaking-up experiences for patient safety among nurses in South Korean. Overall, it is necessary to overcome cultural barriers and establish an environment that encourages speaking up. In addition, developing speaking-up training programs for nursing students and novice nurses is imperative to prevent patient safety incidents.