To achieve the high-efficient and selective flotation separation of scheelite from calcium gangue, mixed depressant, SML/CMC, was designed and used. The novel depressant was biomass-based and eco-friendly. It consists of sulfomethylated alkali lignin and sodium carboxymethyl cellulose with the mass ratio of 5:1. The synergistic effect of the depressants were explored. With the mixed depressant, the recovery of scheelite reached 81.23 % with 50 mg/L of SML/CMC at pH = 11, while the recoveries of fluorite and calcite were 3.63 and 14.70 %, respectively. The contact angle, zeta potential, FTIR, and XPS were used to compare the changes in surface properties of the minerals caused by SML/CMC. The calcium ions on mineral surfaces were the main active sites for the adsorption of SML/CMC. The depressing effect of SML and CMC on calcite gangue was attributed to the reaction between calcium ions and functional group of SO32- and-RCOO-. The novel and biobased mixed depressant, SML/CMC, exhibited higher selectivity, as it integrated the high selectivity of SML and the strong depressing ability of CMC. With the mixed depressant, the separation of scheelite from fluorite and calcite was improved. The research provided a kind of green depressant for high-efficiency recovery of scheelite, as well as the basis for design of high-efficiency depressant.