Objective: To explore the longitudinal changes and related predictive factors of anxiety and intolerance of uncertainty (IU) among Chinese college students, so as to provide theoretical reference for promoting students mental health. Methods: Intolerance of Uncertainty Scale-short Form and the 7 item Generalized Anxiety Disorder Scale were administered among 5 683 students from 22 universities in Guangdong Province from September 10 to October 17, 2021 (T1, baseline survey), and from March 15 to April 22, 2023 (T2). Using paired sample t-test to analyze the changes in anxiety and IU among college students, a linear regression model was established to explore factors that can predict anxiety, IU and their changes during T1 and T2 periods. Results: During the T1 period, the average scores of anxiety and IU among college students were (3.26±3.46, 34.88±7.96), while during the T2 period, they were (4.41±4.16, 36.40±8.07). During the T2 period, the levels of anxiety and IU among college students were higher than those during the T1 period ( t=19.59, 13.67, P <0.01). The linear regression results showed that age ( B = -0.02 ), moderate ( B =-0.18) and poor ( B =-0.88) mental health status, as well as online browsing of Corona Virus Disease 2019 (COVID-19) epidemic (later called as epidemic) related information for >1-<3 hours ( B =-0.30) and ≥3 hours ( B =-0.22), all of which could negatively predict changes in anxiety during T1 to T2 periods. Living in rural areas ( B =0.11) could positively predict changes in anxiety during T1 to T2 periods ( P <0.05). Moderate ( B =-0.19) and poor ( B =-0.47) mental health status, browsing epidemic related information online for >1-<3 hours ( B =-0.32) and ≥3 hours ( B =-0.33), academic performance being moderately affected by the epidemic ( B =-0.10), and personal planning being moderately affected by the epidemic ( B =-0.13) and severely affected ( B =-0.22), all of which could negatively predict changes in IU during T1 to T2 periods ( P <0.05). Conclusions Levels of anxiety and intolerance of uncertainty increases significantly after epidemic. Mental health status of college students should need long term monitoring, and students with poor mental health should need special attention.