For development of proton conductive membranes, it is a difficult dilemma to balance proton conductivity and methanol permeability; however, this research proposes a simple strategy to solve this problem, i.e., embedding a proton conductive "barrier" into the perflorosulfonated matrix. The strategy is exemplified by embedding the amphoteric sulfonated poly(phthalazinone ether sulfone kentone) (SPPESK) into a semicrystalline perflorosulfonic acid polymer matrix (FSP). After being annealed, the domain of SPPESK is converted to the barrier. Two acid-base interactions constitute the barrier for both the transfer of protons and the blockage of methanol, respectively. On one hand, poorly hydrophilic ionic acid-base interactions (-SO(3)(-)...NH(+)-) are formed between sulfonic acid group and phthalazinone group through annealing and are useful for methanol blocking. On the other hand, more hydrophilic hydrogen-bonded acid-base interaction (-SO(3)H...(H(2)O)(n)...N-, n ≤ 3) can also be formed under hydrated condition and facilitate proton transport according to the Grotthuss-type mechanism. As a result, the final membrane exhibits an extremely low methanol permeability (30% of that of Nafion-112) and an excellent fuel cell performance (as compared with Nafion-112 at 80 °C).