To address the problems of asymmetric deformation and support optimization caused by excavation mutual interference in twin-tunnels with asymmetric weak surrounding rock, based on Dongmachang No.1 tunnel of Huali Expressway in the western mountainous areas, a combined method of on-site monitoring, model tests, and FLAC^3D numerical simulation was adopted. The results are as follows: Starting the excavation on the weaker side can reduce the settlement of the arch top on the weaker side by 16.4%, effectively lowering the risk of significant deformation. Under the differential support, on one hand, the support of the softer side is strengthened, increasing the overall capacity of the softer side support by 30% to 50%, making the distribution of the surrounding displacement of the two tunnels more uniform, and significantly improving the force-bearing condition of the softer side support structure. The bending moment of the arch top of the softer side decreases by 17.8% and the axial force decreases by 19.4%. On the other hand, within the 2.0D(D represents the diameter of the single tunnel excavation) net distance, the active reinforcement of the advance tunnel support has a “protection effect” on the subsequent tunnel. At a 0.5D net distance, the horizontal convergence of the upper step decreases by 14.70%. When the net distance increases to 4.0D, the effect can be ignored. The sensitivity of the more weak side to the adjustment of support parameters is 1.8 to 3.2 times that of the less weak side. The control efficiency of the surrounding displacement of the tunnel in the stages of 3-6 m for the anchor rods, 26-31 cm for the primary support, and 5-10 m for the inverted arch anchor pipes is the best. The optimized parameter range of this support can be directly applied to the construction of similar tunnels in soft and uneven ground layers, significantly reducing the risk of large deformation and engineering costs. It can be seen that for the double-tunnel tunnels with left and right weak and uneven soft rocks, adopting the design of supporting parameters for the less weak side first and the differentiated design can effectively suppress asymmetric deformation, and improve the safety and stability of the tunnel structure.