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In view of the fact that the bacterial concentration of the fermentation process in the Marine Lysozyme in difficult to be detected online and the off-line measurement cannot reflect the the change of the parameters in time, a new method of soft sensor modeling which is based on improved Krill Herd algorithm (KH) and improved adaptive fuzzy neural network is proposed. Firstly, the adaptive levy flight strategy is used to improve the global KH search and the HOT is used to improve the local search capabilities; Then the improved KH is used to reduce over correction and large calculation in the adaptive fuzzy neural network; Finally, the soft sensor prediction model based on HLKH-ANFIS of bacterial concentration in ML fermentation process can be established. The simulation result show that the improved model has smaller error and better prediction performance than KH-ANFIS, which can meet the online prediction demand of the key parameters in ML fermentation.