In this paper, attitude control of rigidliquidflexible multibody coupling spacecraft with unknown interference and uncertain parameters is studied. The sloth of liquid fuel is equivalent to the spherical pendulum model, the flexible attachment is assumed to be Euler-Bernoulli beam, and the dynamics equation of spacecraft is established by Lagrangian method. Firstly, an integral sliding mode disturbance observer was designed for a finite time, enabling the designed model to estimate the lumped disturbances of the control system within a specified time range. Then, based on disturbance observer, a timevarying sliding mode control method is designed, which uses hyperbolic tangent function. Finally, a zerovibration command smoothing device is designed to suppress liquid sloshing and vibration of flexible accessories. The numerical simulation results indicate that the control scheme designed in this paper is feasible and effective, the residual vibration caused by the multimode flexible spacecraft during attitude maneuver can be effectively suppressed.