The loader is a widely used type of high-power construction machinery, so reducing its interior noise can greatly improve the man-machine environment. Models of a loader cab and its acoustic cavity are built separately to compose an acoustic-structural coupling model that is verified by single input and multiple output (SIMO) mode test. The excited force of the suspension points is measured. Then, the frequency response analysis and the prediction of the cab interior noise are carried out. Acoustic sensitivity analysis and the acoustic panel contribution of the cab are performed using the acoustic transfer vector method. Topography optimization is carried out on the critical panels based on the acoustic panel contribution analysis. Then, rubber damping material is applied to reduce the vibration. Finally, the second prediction of the virtual pressure is carried out. The acoustic sensitivity analysis can obtain several critical vibro-acoustic coupling frequencies, and the panel contribution analysis based on the acoustic transfer vector method can determine the critical panels that accurately produce the noise peak values. In addition, the scheme of the topography optimization and rubber damping materials has a remarkable effect on noise reduction, and the overall sound pressure level dropped by 4.43dB. This scheme provides a technical route to design a low noise car body systematically, decrease the subjectivity and repetitions of the traditional process, reduce design costs, and shorten the design cycle.