Objective To establish an animal model of infecting Syrian golden hamsters with CVB1(Coxsackievirus B1, CVB1). Methods Syrian golden hamsters were infected with CVB1 by intranasal instillation at a dose of 107. 25 CCID50, and were observed clinically for 14 days during which throat swabs, nasal lavage fluid and feces were collected and tested daily for viral load. On the 7th day of infection, 3 hamsters were euthanized, and blood samples were collected for viral load and biochemical detection. At the same time, tissue samples were collected for viral load, histopathology and IHC detection. Results The animals infected with CVB1 virus showed varying degrees of listlessness, decreased body temperature, and typical red rash and herpes on the mouth within 14 days, similar to the clinical manifestations of human HFMD. Viruses could be detected in throat swabs, nasal lavage fluid, stool, and blood; viral load was detected and viral antigen was observed in the tissues, accompanied by pathological changes such as inflammation, hyperplasia and hemorrhage; liver functional and myocardial enzymes in serum increased. Conclusions The model of infecting Syrian golden hamsters with CVB1 virus by nasal drip showed pathological damages of tissues and organs such as myocardium and liver, which indicates that the model can be used for the study of human hand-foot-mouth disease.