Renewable natural fibers (e.g., cellulose nanocrystals (CNCs)) are being applied for reinforcing bio-based polylactic acid (PLA). For improvement in the interfacial compatibility between CNCs and PLA and the dispersibility of CNCs, a quaternary ammonium salt-coated CNCs (Q-CNCs) hybrid was prepared in this study based on an esterification self-polymerization method, and such hybrid was further utilized as a new strengthening/toughening nanofiller for producing the Q-CNCs-reinforced PLA composite. The results confirmed that quaternary ammonium salt coatings could efficiently enhance CNCs/PLA interfacial compatibility via mechanical interlocking and semi-interpenetrating networks. Attributing to the synergistic effect of quaternary ammonium salts and CNCs, a considerable enhancement in processing, mechanical, and thermal properties was gained in the obtained Q-CNCs-reinforced PLA composite. With the addition of 0.5 wt% Q-CNCs, the tensile strength, Young's modulus, and elongation at break of the Q-CNCs-reinforced PLA composite was raised by approximately 23 %, 37 % and 18 %, respectively; compared with pure PLA, the obtained composite had excellent bacteriostatic properties and good transparency. This work discusses the development of high-performance, low-cost and sustainable PLA-based composites on a potential application in packaging materials.