Cancer is a worldwide leading cause of death. Conventional therapeutic techniques for cancers have some obvious limitations and are unsatisfactory, thus it is very necessary to develop new therapy technology. Recently, near-infrared (NIR) laser-induced photothermal ablation therapy (PAT) has been demonstrated to have great potential to cure tumors, and a prerequisite is to obtain biocompatible and efficient photothermal agents. Among all the photothermal agents, semiconductor-based photothermal nanoagents have attracted increasing interest due to their low cost and high photothermal conversion efficiency. This review attempts to summarize the recent progress in the rational design and fabrication of semiconductor photothermal nanoagents, including Cu-based (CuS, Cu9S5 and CuSe) and W-based (W18O49, CsxWO3 and WS2) nanomaterials. Furthermore, the semiconductor-based multifunction nanoagents (such as G-CuS-DOX, FeS2-350) are also summarized for the development of synergic photothermal/chemo-therapy or imaging-guided photothermal therapy. This review ends with a summary and some perspectives on the challenges and new directions in this exciting and still emerging area of research.