The problem of clathrate hydrate plugging in flow pipes has been the most important issue in the off-shore exploitation since hydrates were found in transport facilities. In recent years, low dosage hydrate inhibitors have attracted much interest among researchers in place of thermodynamic hydrate inhibitors such as methanol and mono ethylene glycol (MEG). Poly-vinyl caprolactam and poly-isopropylacrylamide (PNIPAM) are among the hydrate inhibitors that are typically used for polymers containing amide groups. Furthermore, various kinds of polymer inhibitors containing amide group including tetrabutylphosphonium bromide(TBPB), which is a quaternary salt, were synthesized and studied in a methane gas hydrate environment. In this experiment, the injection of 0.1 wt% inhibitor at 276 K and 5 MPa was followed by stirring the water to induce nucleation. From the result, when PNIPAM alone was used as a single KHI, PNIPAM exhibited worst performance among the KHIs tested in this study. But the mixing of TBPB with PNIPAM further extended the induction time and reduced the CH4 hydrate growth rate. The real-time in situ Raman system used to understand the inhibition principle was recorded during CH4 hydrate formation, as a result, PNIPAM showed that the large hydrate cage affected, while TBPB prevented the CH4 molecule from occupying the small cage. TBPB was excellent synergist in blends with PNIPAM for kinetic hydrate inhibition of structure I forming CH4 hydrate.