The invention belongs to the technical field of small molecular photo-thermal materials, particularly relates to a thiazole orange derivative, preparation and application thereof, and provides a thiazole orange derivative, which has a structure represented by a formula I, wherein n is equal to 1, 2 or 3, X is I, Br or Cl, R1 is fatty acylamino, fatty carboxyl or fatty alkyl, and R2 is triphenyl phosphine or triphenyl amine. The invention also provides a preparation method of the thiazole orange derivative. The preparation method comprises the following steps: reacting a compound with a structure epresented by a formula IX with a compound with a structure represented by a formula VII to obtain a compound with a structure represented by a formula I, wherein n is equal to 1, 2 or 3, R2 is triphenyl phosphine or triphenyl amine, Y is I, Br or Cl, X is I, Br or Cl, and R1 is fatty acylamino, fatty carboxyl or fatty alkyl. The invention discloses an application of a thiazole orange derivative in preparation of a targeted photothermal therapy tumor drug or a targeted photoacoustic imaging signal drug.