Objective: To explore the association of the frequency of domestic violence witness in childhood with the quality of life (QOL) of college students, and to provide a reference for improving the quality of life of students who domestic violence witness in childhood. Methods: In October 2018, a total of 4 034 college students from four universities in Hefei, Anhui Province, were selected to participate in this study. The Conflict Tactics Scales Short Form (CTS2SF) and the World Health Organization Quality of Life-Brief (WHOQOL-BREF) were used to assess the effect of witnessing domestic violence in childhood on the QOL of college students. Multiple linear regression was used to analyze the relationship between the different frequencies of witnessing domestic violence in childhood and the QOL of college students. Results: The mean scores of the subjective assessment of QOL, health subjective assessment, physiology, psychology, social relationships, and environment were (14.06±3.25) (13.42±3.47) (12.61±2.02) (14.09±2.62) (13.72±2.71) (13.77±2.46), respectively. The multiple linear regression model showed that, witnessing domestic violence in childhood was negatively correlated with the QOL of college students (P<0.01). Although occasional expose to severe family violence in childhood was not associated with the health subjective assessment and the environmental dimensions, the different frequencies of witnessing domestic violence in childhood were negatively correlated with the QOL of college students (P<0.05). Conclusion Frequency of domestic violence witness in childhood is associated with the mean scores of the QOL of college students. It is necessary to explore effective prevention and intervention programs for exposure to domestic violence in childhood.