Excessive accumulation of fat cells leads to obesity—a predominantly urban public health concern. Photothermal therapy (PTT) can be a novel strategy to control the fat droplets using deep penetrating infra-red light absorption in upconversion nanoparticles (UCNPs). First, silica (SiO2) coated UCNPs embedded in commercial butter is shown to demonstrate photothermal heating (with photothermal conversion efficiency ≈60%) to gain a maximum temperature rise of ≈26 ºC (to 50 ºC) when exposed to 980 nm laser (5 min, 1 W) irradiation that melts the butter. The same UCNPs @SiO2 are used to study the PTT effect in mouse 3T3 cell derived fat cells in vitro. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay on differentiated 3T3 cells reveals low cytotoxicity (cell viability >70%) up to 400 ppm concentration of the UCNP@SiO2. Absorption studies on Oil Red O stained fat droplets, in 3T3 cells incubated with 50 ppm (50 μL) of UCNP@SiO2, shows 50% (untreated control = 100%) decrease of the 510 nm band post irradiation indicating ≈50% of droplet disintegration by PTT. Time lapse videography shows severe droplet agitation resulting in cytoskeletal re-arrangement in the irradiated, as well as only resistively heated cells with the UCNPs confirming a thermal effect.