In this paper, a J-integral formula and numerical calculation method are presented, which confirm the path-independence of a J-integral, considering the mixed-mode fracture in a chemo-mechanical coupled medium. The Jk-integral denotes a two-dimensional vector consisting of the components J1 and J2. Using the Equivalent Domain Integral (EDI) method, the chemo-mechanical coupled J2-integral, with an equivalent domain form that includes both a surface integral and a line integral, is deduced using a poroelastical model. Based on a semi-analytical method, an auxiliary J¯2-integral is derived to develop a finite element calculation program. By choosing two characteristic lengths, near the crack tip, the mixed-mode fracture parameters, KI, KII and Ts (T stress) at the crack tip, can be calculated. The mixed-mode fracture problems, which are related to center-cracked and edge-cracked plates, are numerically studied for certain chemo-mechanical coupled boundary conditions. The accuracy of this method is verified with numerical examples, which shows the path-independence of the J-integral for chemo-mechanical coupling. The stress fields of two different cracked hydrogel plates are analyzed with different boundary conditions under the chemo-mechanical coupled mixed-mode fracture. This work provides new insights into the mixed-mode fracture mechanics of a chemo-mechanical coupled medium.