Abstract The reactive oxygen species (ROS) serve a significant role in cancer therapy due to their oxidative capabilities to modulate cellular functions from homeostasis to apoptosis. While conventional noble metal nanoparticles exhibit superior biocatalytic efficacy in ROS induction, their indistinctive toxicity toward cells and organisms limit their potential for targeted cancer therapy. Here, ultrathin biocompatiable molybdenum oxides (MoO x ) nanodots are explored that simultaneously incorporate hydrogen (H + ) and ammonia (NH 4 + ) dopants, subsequently their electronic band structures can be modulated by both the relative contents of H + and NH 4 + dopants for efficient generation of ROS. An ultrafast and repeatable dye degredation capability in the absence of light is find in MoO x doped with low H + and high NH 4 + , in which hydroxyl radicals (·OH) is identified as the agent stimulating this ROS‐driven process through scavenger analysis. More importantly, the selective biocatalytic potential of such a multi‐doped MoO x is demonstrated by the comprehensive assay analysis, revealing a three‐fold greater cytotoxicity toward HeLa cancer cells within 24 h compared with those of HEK293T healthy control. The finding shines a light on the targeted cancer therapies that spare healthy cells, showing the potential of multi‐doped metal oxide as a biocompatiable alternatives to noble metals in selective cytotoxicity against tumor cells.