As a green and inexpensive biocatalyst, lipase has been used to catalyze the synthesis of 3,3′-(arylmethylene)bis(2-hydroxynaphthalene-1,4-dione) (3) for the first time. The products could be obtained in excellent yields (82.2–94.8%, 2 h). This study not only provides a simple and efficient method, but also expands the biocatalytic promiscuity of lipase in organic synthesis.