Cell disruption is a key unit operation when an intracellular target product has to be recovered for further downstream processing. A wide variety of chemical, biological, physical, and mechanical methods are available to release biological products from the cell factories. Among them, high-pressure homogenization (HPH) is recognized as one of the most promising methods due to its efficiency, reproducibility, scalability, and relative easiness. In this chapter, a guide to applying HPH in the cell factory Komagataella phaffii is presented.