Objective To explore the moderating effect of workplace spirituality between challenge-hindrance stressors and safety behavior among junior nurses, so as to provide references for nursing managers to develop safety behavior management strategies for junior nurses.Methods A total of 390 junior nurses from 10 general hospitals in Henan province were selected, then they were surveyed by using a general information questionnaire, the Nurse Safety Behavior Scale, the Challenge-hindrance Stress Scale, and the Workplace Spirituality Scale.Results The participants′ safety behavior was （56.54±4.37） points, challenge stress was （21.09±5.52） points, hindrance stress was （15.07±5.38） points, workplace spirituality was（110.66±20.01） points.Junior nurses′ safety behavior was negatively correlated with hindrance stress, and it was positively correlated with challenge stress and workplace spirituality (all P＜0.05).Workplace spirituality played a significant moderating effect between challenge stress and nurse safety behavior （P＜0.05）, but it didn′t play a moderating effect between hindrance stress and nurse safety behavior （P＞0.05）.Conclusion Junior nurses′ safety behavior is at a medium and above level, and challenge-hindrance stressors are bidirectional predictors of safety behavior, and workplace spirituality could enhance the positive effects of challenge stress on junior nurses′safety behavior.Therefore, nursing managers can enhance the safety behavior of junior nurses by identifying and managing work-related stressors and fostering workplace spirituality.