Abstract: Objective To analyze the epidemiological and etiological features of hand-foot-and-mouth disease (HFMD) in Longhua district, Shenzhen City, in order to provide an important scientific basis for the HFMD prevention and control strategies in this area. Methods HFMD epidemiological data of Longhua district was obtained from China's disease prevention and control information system; The nucleic acid of enteroviurs (EV), enteroviurs 71(EV-A71)and coxsackievirus A16(CV-A16)for 447 cases of HFMD in Longhua district was detected by fluorescent quantitative reverse transcription-polymerase chain reaction(RT-PCR),and VP1 of non EV-A71, non CV-A16 and other EV was performed sequencing to identify the subtype and carry out evolutionary analysis. χ² test was used to analyze the results of HFMD pathogen typing between different age group. Results The high incidence of HFMD in Longhua district of Shenzhen City was Longhua street and Guanlan street. The incidence curve showed a bimodal distribution, the main peak in May-July, the second peak in September-November. Children under 5 years of age was 96.40% among all incidence. There was significant difference in different age groups of HFMD pathogen typing(χ²=25.01,P<0.001). Conclusions CV-A6 is the main pathogen of HFMD in Longhua district of Shenzhen, and there are two main branches in evolutionary relationship in 2015. However, there are multiple branches in CV-A6 in 2016. HFMD prevention and control should focus on children under the age of 5.