High-solid and multi-phase bio-reaction refers to the system with more than 20% solid loading which has the potential in making lignocelluosic biomass usage commercially and environmentally accessible. However, high solid-to-water ratio leads to problems concluded as “solid effects” (including production inhibition, invalid enzyme adsorption and water constraint), thus affecting biomass conversion correspondingly. Moreover, changeable rheology caused by high solid loading makes it ill-suited when applying traditional strengthening strategies to high-solid and multi-phase bio-reaction. To be exactly, high visicosity resulting in exponential increase in energy input while using mechnical agitation. Shear force caused by mechnical agitation deactivate enzyme and microoganism in high-solid and multi-phase bio-reaction system thus affecting biomass conversion performance. This proposed new requirments for proecess intensification. This paper elaborates specificity of high-solid and multi-phase system and its effects on biomass coversion. Additioanlly, based on several-years studies in our goup, novel potential process intensification strategies (i.e. periodic peristalsis agitation and gas double-dynamic) for high-solid and multi-phase bio-reactionare also discussed, expecting to provide perspective of process engineering in recognizing high-solid and multi-phase bio-reaction.