Objective To investigate compliance to home quarantine protection and its effect on anxiety degree of the public during coronavirus disease 2019(COVID-19) epidemic outbreak period. Methods Using cross-sectional research method, questionnaire was sent to WeChat and friends circle through questionnaire star, and online investigation was conducted anonymously, investigation time was from February 4 to 6, 2020. The self-designed questionnaire of general information, questionnaire of knowledge, attitude, and practices (KAP) of home quarantine protection, and the self-rating anxiety scale(SAS) was used to investigate the compliance and anxiety degree of home quarantine protection. Results A total of 454 persons were investigated. SAS of the respondents was (38.74±8.46), which was higher than that of the Chinese norm (P<0.05). The scores of KAP were:awareness of knowledge (24.70±3.96), belief attitude (12.75±1.10), practice compliance (65.54±5.02); compliance rate of practice was 93.63%. SAS of different COVID-19 epidemic relevant population, the number of person staying at home, whether contacted with infected or suspected patients were all statistically different (all P<0.05). Compliance scores of persons of different age, marital status, educational degree, occupation, and persons relevant to COVID-19 epidemic were all statistically different (all P<0.05). There was a negative correlation between SAS and belief attitude and practice compliance (P<0.01); there was a positive correlation between awareness of knowledge and belief attitude (P<0.01); there was a positive correlation between belief attitude and practice compliance (P<0.01). Conclusion The anxiety of public during home quarantine protection period is obvious, and has a close relationship with the knowledge, belief attitude and practice compliance of the public during home quarantine protection period.