Abstract: Objective To understand the reason for sudden increase of human brucellosis cases, infection source and related risk factors in Mudan district of Heze, Shandong province in 2016, and provide evidence for the targeted prevention and control. Methods Active case finding were conducted in local hospitals and affected villages, the incidence data of human brucellosis reported by local medical facilities were collected through communicable disease reporting system, field survey and face to face or telephone survey were conducted, and case sample detection was completed. Results A total of 170 human brucellosis cases were identified in the district, in which 99 (58.24%) occurred during October-December. And 130 (76.47%) cases were the villagers of two Hui ethnic villages. For these two villages, there was a live sheep market with daily trading volume of 1 000 sheep. The sheep sold in the market were mainly from the provinces with high incidence of brucellosis (80.00%). In September, the sheep trading volume increased by 2 times due to Dasain festival. The attack rates were 34.82% (122/3 504) and 0.02% (1/3 608) respectively in those with or without contact with raw mutton, the difference was significant(2=124.782,P=0.001). In the villagers aged 14 years, the attack rate was 17.28% (108/625) in those with contact with sheep (trading, slaughtering, fur processing and raising) and 0.30% (15/5 065) in those without contact with sheep (RR=58.349, 95%CI: 34.220－99.492). The relative risks (RR) for brucellosis in those engaged in sheep trading, slaughtering, fur processing and raising were 84.417(45.925-155.172),80.604(45.209-143.713),43.414(23.450-80.374) and 40.098(20.757-77.459) respectively. When contacting sheep, only 5.13% (8/156) of the cases worn face masks and 21.15%(33/156) of cases worn woolen gloves. Conclusion Contact with sheep from enzootic areas and lacking of effective personal protections were the risk factors for this outbreak. It is suggested that the sheep of endemic area should be vaccinated and the sheep unvaccinated should not be sold in markets. The sheep quarantine and self-protection should be strengthened.