Efficient porcine interferon-a(pIFN-a) expression in high density recombinant Pichia pastoris cultivation was achieved in a 5 1 bench-scaled bioreactor. The resultsindicated that a high and stable oxygen uptake rate (OUR)during induction phase was closely related with pIFN-aproduction efficiency.The multi-variables clustering andanalysis results showed that the achievement of a high andstable OUR relied on a higher glycerol consumption rateduring fed-batch culture phase and a moderate methanollevel (around 10 g/l) during induction phase. In the highand stable OUR environments (200-300 mmol/l/h), thehighest pIFN-a antiviral activity could reach a level of 6.7 x 10 IU/ml, which was morethan 10-300-folds higherthan those obtained at lower OUR (80-200 mmol/l/h) usingthe same bioreactorand those obtained in shaking flasks.Clustering and analysis of the specific growth and glycerolconsumption rates data during culture phase could detect the ill fermentation state at early stage, potentially provided a simple and effective fault alarming/diagnosis method for the achievement of stable pIFN-a production.