Hand, foot, and mouth disease (HFMD) has been one of the most common infectious diseases in Shijiazhuang City, as is the situation in China overall. In the National HFMD surveillance system, the pathogen detection was focused on EV-A71 and CVA16, and therefore, information on the other EVs is very limited. In order to identify the circulating EV serotypes in the HFMD outbreaks in Shijiazhuang City during 2010-2012, 4045 patients presented with HFMD were recruited in the study, and clinical samples were investigated. Typing of EV serotypes was performed using the molecular typing methods, and phylogenetic analyses based on entire VP1 sequences of human enterovirus 71 (EV-A71), coxsackievirus A16 (CVA16), CVA10 and CVB3 was performed. The results revealed that EV-A71 and CVA16 were the 2 most important pathogens but the circulating trends of the 2 viruses showed a shift, the spread of EV-A71 became increasingly weak, whereas the spread of CVA16 became increasingly stronger. CVA10 and CVB3 were the third and fourth most prevalent pathogens, respectively. Co-infection of two viruses at the same time was not found in these samples. Based on entire VP1 region sequences, the phylogenetic analysis revealed that C4a subgenotype EV-A71, B1a and B1b subgenotype CVA16 continued to evolve. The CVA10 strains were assigned to 4 genotypes (A-D), whereas the CVB3 strains were assigned to 5 genotypes (A-E), with clear geographical and temporal-specific distributions. The Shijiazhuang CVA10 sequences belonged to 4 epidemic lineages within genotype C, whereas the Shijiazhuang CVB3 sequences belonged to 2 epidemic lineages within genotype E, which may have the same origins as the strains reported in other part of China. CVA10 and CVB3, 2 pathogens that were previously infrequently detected, were identified as pathogens causing the HFMD outbreaks. This study underscores the need for detailed laboratory-based surveillances of HFMD in mainland China.