Nanostructures of metal oxide semiconductors play significant roles in a variety of areas, such as biotherapy, pollutant treatment and energy storage and conversion. The molybdenum oxide (MoO) nanostructures have shown promising applications especially when used as photothermal treatment agents due to their relatively low cost, facile synthesis and low toxicity. However, the design and synthesis of efficient MoO nanomaterials with tunable phases and morphologies for theragnosis of tumors remains a challenge. In this work, hydrophilic MoO with controlled structures and phases was synthesized by a simple one-step hydrothermal process. The as-obtained MoO nanoclusters showed a desirable size of ∼40 nm in diameter exhibiting unique properties as a theragnosis nanoplatform: (1) strong near-infrared absorption, which is due to oxygen vacancies of the nanoclusters, as proved by photoluminescence spectroscopy and X-ray photoelectron spectroscopy; (2) excellent photothermal performance with a photothermal conversion efficiency of up to 62.1%; and (3) the image response of X-ray computed tomography (CT) and infrared thermal imaging for simultaneous diagnosis of tumors. This study provided the facile synthetic strategy for controllable metal oxide semiconductors and promoted the development of metal oxides for theragnosis therapy of cancers.