Vertically oriented interstitial atom carbon-anchored molybdenum disulfide (C-MoS) nanospheres loaded with iron oxyhydroxide (β-FeOOH) were proposed for modulating the surface catalytic activity and stability of the unsaturated catalytic system. The β-FeOOH@C-MoS efficiently activated peroxymonosulfate (PMS) to degrade 95.4% of tetracycline (TC) within 30 min, owing to the more sulfur vacancies, higher surface hydroxyl density, redox ability and electronic transmission rate of β-FeOOH@C-MoS. According to the characterization and analysis data, the multiple active sites (Fe, Mo and S sites) and oxygen-containing functional groups (CO, -OH) of β-FeOOH@C-MoS could promote the activation of PMS to form reactive oxygen species (ROS). The oxidation cycle of Fe(II)/Fe(III) and Mo(IV)/Mo(VI), the electron transfer mediator of rich sulfur vacancies, as well as oxygen-containing functional groups on the surface of β-FeOOH@C-MoS synergistically promoted the formation of ROS (O, FeO, SO and •OH), among which O was the main active oxidant. In particular, the β-FeOOH@C-MoS/PMS system could still degrade pollutants efficiently and stably after five recycling cycles. Furthermore, this system had a strong anti-interference ability in the actual water body. This study provided a promising strategy for the removal of difficult-to-degrade organic pollutants.