Nattokinase(EC3.4.21.62) is a kind of serine proteinase that has potent thrombolytic activity.Compared to the first-line thrombolytic drugs(urokinase and streprokinase),nattokinase possesses several advantages such as safety,low cost,long half-life and easy oral administration.Therefore,nattokinase has been receiving increasing attention for its use as thrombolytic agent or health care product.The solid and liquid fermentation sare usually employed for the nattokinase production.However,the fermentation titer of nattokinase is still poor,and can meet the requirement of the market.In this review,the strain breeding,medium optimization,fermentation conditions optimization,and culture mode of nattokinase have been outlined and summarized,which would provide valuable reference for the industrial production and application of nattokinase.