Due to their unique characteristics, gallium-based liquid metal (LM) nanoparticles have been applied in various research fields. LM nanoparticle surface-modification design is essential for enhancing the original LM properties and physicochemical multifunctionalization. This study developed core-shell type nanoparticles based on eutectic gallium-indium and various biomolecules such as gelatin, deoxyribonucleic acid, lecithin, and bovine serum albumin using a sonicator and γ-ray radiator. In particular, the synthesized gelatin-functionalized LM nanoparticles exhibited excellent water dispersibility, unique morphology, uniform particle size, low toxicity, characteristic optical absorbance, potent photothermal conversion, high intracellular penetration, powerful photothermal anticancer efficacy, and functionalization with a fluorescent probe via dehydration condensation. The synthesized functional LM nanoparticles displayed in vivo fluorescent diagnosis of the targeted tumor location due to the enhanced permeability and retention effect. Moreover, the photothermal function of the LM nanoparticles was spatiotemporally activated by a biologically penetrable near-infrared laser to trigger targeted tumor ablation in mice. Thus, this study has provided an LM platform to design an effective, authentic nanoparticularization method and advance optotheranostics in cancer treatment.