Photoacoustic imaging and photothermal therapy that employ organic dye in the second near-infrared window (NIR-II) became an attractive theranostical strategy for eliminating solid tumors, in which IR1048 was previously reported to be a good candidate. However, the further biomedical application of IR1048 was blocked by its poor water-solubility and lack of tumor-targeting. To solve this problem, liposome camouflaged with 4T1 cell membrane fragments was employed to encapsulate IR1048 (thereafter called MLI), and its application for photoacoustic and thermo-imaging and photothermal therapy were explored in vitro and in vivo. The results showed that MLI exhibited spherical morphology around 92.55 ± 5.41 nm coated by monolayer adventitial fragments, and uniformly dispersed in PBS with high loading efficiency and encapsulation efficiency to IR1048. In addition, both free IR1048 and MLI presented strong absorption in NIR-II, and upon 1064 nm laser irradiation the MLI showed awesome photothermal performance that could rapidly elevate the temperature to 50.9C in 6 min. Simultaneously, phantom assay proved that MLI could dramatically enhance the photoacoustic amplitudes by a linear concentration-dependent way. Moreover, either flow cytometry or confocal analysis evidenced that MLI was the most uptaked by 4T1 cells among other melanoma B16 cells and Hek293 cells and coexist of IR1048 and 1064 nm laser irradiation were indispensable for the photothermal cytotoxicity of MLI that specifically killed 96.16% of 4T1 cells far outweigh the B16 cells while hardly toxic to the Hek293 normal cells. Furthermore, PA imaging figured out that 4 h post tail-vein injection of MLI was the best time to give 1064 nm irradiation to conduct the photothermal therapy when the average tumor-accumulation of MLI achieved the highest. In the NIR-II photothermal therapy, MLI could significantly inhibit the tumor growth and almost ablated the tumors with slight body weight variation and the highest average life span over the therapy episode and caused no damage to the normal organs. Hence, MLI could pave the way for further biomedical applications of IR-1048 by homologous tumor-targeting and dual-modal imaging directed NIR-II accurate photothermal therapy with high efficacy and fine biosafety.