Titanium nitride, an alternative plasmonic material to gold with unique physiochemical properties, has been widely used in microelectronics, biomedical devices and food-contact applications. However, its potential application in the area of biomedicine has not been effectively explored. With the spectral match of their plasmon resonance band and the biological transparency window as well as good biocompatibility, titanium nitride nanoparticles (TiN NPs) are promising photoabsorbing agents for photothermal therapy (PTT) and photoacoustic imaging. Nevertheless, the photothermal performance of TiN NPs has not been investigated until now. Here, we presented the investigation of employing TiN NPs as photoabsorbing agents for in vivo photoacoustic tomography (PAT) imaging-guided photothermal cancer therapy. Our experimental results showed that TiN NPs could strongly absorb the NIR light and provided up to 48% photothermal conversion efficiency. After PEGylation, the resultant nanoparticles demonstrated improved physiological stability and extensive blood retention. Following intravenously administration, they could simultaneously enhance the photoacoustic signals of the tumor region and destroy tumors in the tumor-bearing mouse model by taking advantage of the photothermal effect of the TiN NPs. Our findings highlighted the great potential of plasmonic TiN NPs in detection and treatment of cancer.