Red algae represents an important marine bioresource. One high-value utilization of red algae is the production of agaro- oligosaccharides which have many positive biological effects. However, the lack of an efficient production route seriously limits the application of agaro-oligosaccharides. In this study, we established a green route that combines chemical liquefaction and enzymatic catalysis for the efficient production of agaro-oligosaccharides, and we used the production of neoagarotetraose (NA4) as an example. Agarose (150gL?1) liquefaction by citric acid was controlled with respect to two targets: a 100％ liquefaction rate and a high average degree of polymerization (>4) of the liquesced agaro-oligosaccharides, which were then catalyzed byβ-agarase into an oligosac- charides mixture with a high concentration of NA4 (30.8gL?1) in a 1-L reaction volume. After purification, we obtained 25.5g of NA4 with a purity of 92％. This work establishes an easy route for the efficient production of pure agaro-oligosaccharides from agarose.