The invention discloses a design method for shear resistance of an orthotropic steel-mixed composite bridge panel interface. The orthotropic steel-mixed composite bridge panel interface stressed spatially is equivalent to continuous beam on multiple supports stressed in a single direction and the interlaminar shear force is calculated, so that anti-shear connectors are arranged and designed. The design method comprises the following steps: 1, calculating a mid-span section bending moment linear coefficient (mu) of a wheel load on two cross diaphragm plates; 2, calculating longitudinal calculating width (b0) of the orthotropic steel-mixed composite bridge panel; 3, calculating the equivalent elastic support stiffness (K) of a longitudinal rib; 4, based on the calculating results obtained inthe previous three steps, constructing a cross bridge calculating model of the orthotropic steel-mixed composite bridge; 5, calculating the cross bridge interlaminar stress as shown in the specification by adopting a structural mechanical method; and 6, arranging and designing the shear pieces. The method disclosed by the invention overcomes the defects that a conventional finite element calculating and modeling workload is great and the method does not have universality for different projects, is clear in mechanical concept and high in practicality, and is conveniently applied to anti-sheardesign of the orthotropic steel-mixed composite bridge panel interface.