The grouting consolidation of deep and thick backfill of giant karst of railway tunnel is of great significance. Hence, the grouting reinforcement design of the upper backfill is carried out on the basis of theoretical analysis, and the grouting effect is analyzed through numerical simulation. The analytical results show that the grouting fills the pores of muck backfill to increase the upper load of karst, which plays the effect of compaction and isolates the train′s dynamic load from passing down to prevent the backfill from disturbing settlement after construction. In the practice of grouting engineering, attentions are paid on the grouting quality control to solve the problem of grouting defects caused by the poor forming of the surrounding grouting wall, and realize the dense grouting consolidation in the enclosed area. The grouting effect is tested and evaluated. After the completion of upper grouting construction, the surface settlement of the backfill is monitored, and the monitoring results indicate the feasibility of the karst cave treatment method of muck backfill + upper grouting reinforcement in terms of settlement control.