The stability of underground goaf in filling mining is dominated by the interaction mechanism of the backfill-surrounding rock combination. In order to investigate the interaction mechanism and failure characteristics of the backfill-surrounding rock combination, backfill-red sandstone combinations with three different cement–sand ratios were prepared for uniaxial compression tests. The deformation and failure characteristics of the specimens were analyzed. It was found that at the cement–sand ratio of 1:4, the backfill and red sandstone interacted with and restricted each other, and the through cracks appeared in the whole specimens, which indicated that the backfill and red sandstone can jointly resist external loads and play a role in common bearing. However, with the decrease of the cement–sand ratio, the stress mainly acts on the backfill, and the deformation observed in the backfill is large while there is no obvious rupture in the rock. Based on the failure characteristics and the stress–strain curves of the specimens, the damage constitutive relationship that can describe the failure process and deformation characteristics is proposed. Correlated with the experiment results, the damage constitutive equation is established in three stages including compaction pre-synergy stage, quasi-elastic synergy deformation stage and rupture deformation stage. The failure characteristics observed in each stage are analyzed. The research results are of great significance to accurately understanding the interaction between backfill and surrounding rock, which can be used to design and select the mixture ratio of the filling materials.