Hydroxypropyl methylcellulose (HPMC) propels self-emulsifying drug delivery systems (SEDDS) to achieve the supersaturated state in gastrointestinal tract, which possesses important significance to enhance  oral absorption for poorly water-soluble drugs.  This study investigated capacities and mechanisms of HPMC with different viscosities (K4M, K15M and K100M) to inhibit drug precipitation of SEDDS in the simulated gastrointestinal tract environment in vitro.  The results showed that HPMC inhibited drug precipitation during the dispersion of SEDDS under gastric conditions by inhibiting the formation of crystal nucleus and the growth of crystals.  HPMC had evident effects on the rate of SEDDS lipolysis and benefited the distribution of drug molecules across into the aqueous phase and the decrease of drug sediment.  The mechanisms were related to the formed network of HPMC and its viscosities and molecular weight.  These results offered a reference for selecting appropriate type of HPMC as the precipitation inhibitor of supersaturatable SEDDS.