Hypocrellins is regarded as the new generation of potential photosensitizer in the photodynamic therapy. However, the current production of HA in large quantity is limited, whether extracted from the fruit bodies of Hypcrella bambusae and Shiraia bambusicola, or its fermented mycelia. To break through the bottleneck, we screened over 350 fungal strains from the uncommon moso bamboo (Phyllostachys edulis) seeds, and acquired 14 isolates of Shiraia sp. Hypocrellins were generally extracted from the stroma of S. bambusicola, and however the hypocrellin-producing strains in our study were identified as endophytic fungi, where several of them exhibited significantly high content of hypocrellins. One of them, a newly isolated Shiraia sp. strain ZZZ816 was selected for further research. The hypocrellin production conditions of the strain ZZZ816 under submerged fermentation were optimized by one-factor-at-a-time and orthogonal experiment design. The optimum parameters for the quid fermentation were determined as follows: incubation time (144 h), initial pH (6.0), volume of medium (100/250 mL), rotary speed (130 rpm), mycelial age (60 h) and inoculation level (10%). The optimum culture medium constituents were determined as follows: yeast extract 20g/L, malt sugar 40g/L, FeSO 4 ¢H 2 O 0.5g/L, urea 4.0g/L, MgS0 4 ¢7H 2 0 0.5g/L and initial pH 5.0. Using submerged fermentation of the optimum production conditions, the maximum content of hypocrellin A from the strain ZZZ816 was 921.6 mg/L, more than the other industrial strains published in the previous reports. The results demonstrated that Shiraia sp. strain ZZZ816 could enhance the hypocrellin production tremendously with optimizing the fermentation progress.