Objective: To understand cognitive behavioral responses of college students in Guangxi at the early stage of COVID-19 regarding, and to provide a basis for schools and government to formulate relevant strategies and measures. Methods: An anonymous questionnaire survey was conducted among 69 783 students recruited online from 28 colleges and universities in Guangxi Province, regarding psychological response under public health emergencies. Results: Significant associated were found between the total score of COVID-19 knowledge score and factors scores of optimism, fear, avoidance, help and combat in cognitive behavioral response (r=0.15, -0.01, -0.06, -0.03, 0.28, P<0.05). Gender factors had an impact on all the five factors (Z=-13.67, -2.05, -13.31, -7.15, -24.34, P<0.05). Students with higher education levels and medical students had higher score in optimism and lower score in avoidance.Students with limited activities (β=0.38, 0.38, 0.42, P<0.05) and living in a community with infected cases score higher in factor including fear,escape and turning for help (β=0.14, 0.06, 0.15,P<0.05).optimism was negatively associated with fear among students living in a community with infected cases(β=-0.10,P<0.05). Conclusion Relevant departments need to strengthen science popularization and education, further improve students’ awareness of the epidemic, take scientific prevention and control measures, guide positive cognition, shape positive behavior, strengthen mental health education, and make preparations for the orderly resumption of school after the epidemic.