Objective To understand the relationship between eye strain and eye health behavior in college students learning at home during the period of COVID-19 epidemic, and to provide a scientific reference for improving the hygiene of using eyes among the college students. Methods A cross-sectional study and stratified cluster sampling was used to select 2 671 college students from 8 colleges in Anhui Province during the March 1st to July 1st in 2020, and an online questionnaire was survey included general information, eye strain, and daily eye health behavior. Results The prevalence of eye strain in college students was 69.64%. Multivariable Logistic regression analysis showed that eye strain was correlated with gender, myopia, siesta habit, staying up until 2:00 am, and the use of eye liquid, with OR values(95%CI) were 0.64(0.53-0.76), 1.77(1.42-2.20), 0.71(0.59-0.86), 1.39(1.17-1.65), and 2.18(1.71-2.79), respectively. There was no correlation among daily outdoor activity time, daytime reading time and the occurrence of eye strain(P>0.05). Conclusion During the period of COVID-19 epidemic, eye strain among college students is common. The daily eye health behavior is related to the occurrence of eye strain. Under the special learning context, eye care measures should be encouraged specifically.