Near-infrared (NIR) small molecular organic dyes as photothermal agents for cancer photothermal therapy (PTT) have attracted considerable research attention. Herein, two donor-acceptor-donor (D-A-D) structured NIR dyes, BBTT and SeBTT, are rationally designed, where the only difference is one heteroatom within the acceptor unit varying from sulfur to selenium (Se). More importantly, SeBTT NPs exhibit stronger NIR absorbance and higher photothermal conversion efficiency (PTCE≈65.3%). In vivo experiments illustrate that SeBTT NPs can be utilized as a high contrast photoacoustic imaging (PAI) agent, and succeed in tumor suppression without noticeable damage to main organs under NIR photoirradiation. This study presents an effective molecular heteroatom surgery strategy to regulate the photothermal properties of NIR small molecules for enhanced PAI and PTT.