Abstract: OBJECTIVE To investigate the epidemiology, etiology and VP1 gene characteristics in children with severe hand, foot, and mouth disease（HFMD） in Qiongshan district of Haikou, Hainan Province from 2014 to 2019. METHODS General data of HFMD and severe HFMD cases in Qiongshan district, Haikou, Hainan Province from 2014 to 2019 were collected. Real-time fluorescent reverse transcription-polymerase chain reaction was used to detect the nucleic acids of unclassified enterovirus, coxsackievirus A16（CVA16） and enterovirus 71（EV71）. The VP1 gene coding region was amplified and sequenced. RESULTS From 2014 to 2019, a total of 11,248 cases of HFMD was reported in Qiongshan district of Haikou, Hainan Province, in which 75 cases were severe and 4 cases were dead. The overall incidence of HFMD in Qiongshan district of Haikou, Hainan Province firstly increased and then decreased, and the incidence rate was the highest in 2016. HFMD and severe HFMD cases occurred in each month, with the highest incidence rate during May to August. The proportion of EV71 decreased, while the proportion of other enteroviruses increased over time. The nucleotide and amino acid homologies among 7 strains of EV71 obtained after culturing and isolation were 97.1%～100.0% and 99.1%～100.0%, respectively. Sequences of the 7 strains had the highest homology with C4 a subtype, and the nucleotide and amino acid homologies were 93.8%～96.0% and 99.4%～99.8%. The nucleotide and amino acid homologies of 6 strains of CVA16 obtained and cultured were 97.7%～100.0% and 99.2%～100.0%. The nucleotide and amino acid homologies of the 6 strains were 92.7%～97.2% and 96.5%～99.9%, respectively, with the highest homology with subtype B1 B. CONCLUSION From 2014 to 2019, the incidence of HFMD in Qiongshan district of Haikou, Hainan Province shows a first increasing and then decreasing trend. Besides, the distribution of pathogenic bacteria changes over time. In clinical prevention, the monitoring of pathogenic bacteria should be strengthened, and close observation should be carried out to better control the disease.