Pichia pastoris is easy to genetically manipulate and can be grown to high cell densities, at the same time, P. pastoris is a eukaryote, and thereby has the potential for producing soluble, correctly folded recombinant protein with high yield, so the P. pastoris expression system is an ideal choice for the production of various heterologous proteins. However, at present not all the heterologous proteins can be successfully and efficiently expressed in P. pastoris, as a result, different proteins present different yield levels, bioactivity and stability. Here strategies for reducing proteolytic degradation and improving production of the expressed heterologous proteins are briefly summarized in terms of genetically factors and cultivation level.