The effects of moderate pressure (0.1-2.5 MPa) on viability, cell membrane permeability and catalyzing activity of Absidia coerulea for RSA were investigated. A new method for improving the production of Hydrocortisone (HC) from 17α-hydroxypregn-4-en-3, 20-dione-21-acetate by Absidia coerulea in moderate pressure was developed. The results showed that the morphology of Abasidia coerulea mycelium was changed in moderate pressure, Absidia coerulea mycelium seemed to be loosed, and cell membrane permeability of Abasidia coerulea mycelium was improved. However, the viability of Abasidia coerulea mycelium could keep high level. Moreover, the yield of HC was improved over 1.25-fold as compared with that of the control (untreated cells), to give the yield of HC as 350 mg/l, when the Abasidia coerulea mycelium was treated with 0.5Mpa the atmosphere as the pressure media. Especially, the production of HC with atmosphere as the pressure media (0.5 MPa) could be increased by the addition of H2O2 (60 mmol/l); the relative yield of HC in moderate pressure was enriched by over 4.5% in comparison with the control. The major composition of bioconverted mixture was reduced. It was indicated that the new approach (moderate pressure) obtained in this work possessed a high potential for the industrial production of HC.