Candida antarctica Lipase B (CALB) has a wide range of applications in many fields. In this study, Pichia pastoris was used to express CALB for fermentation tank culture. Sodium dodecyl sulfate (SDS) was used as a surfactant, and foam separation technology was used to explore the best experimental conditions for the harvest of CALB. The results showed that the optimal technological conditions for the foam separation and recovery of CALB were as follows: liquid volume was 150 mL, separating gas velocity was 600 mL/min, pH value was 7, and surfactant SDS concentration was 0.5 mg/mL. Under these conditions, the enrichment ratio of CALB was 0.95, and recovery rate R was 80.32%, respectively, indicating that the foam separation technology is feasible to extract lipase B.