The use of lasers has emerged to be highly promising for cancer therapy modalities, most commonly, the photothermal therapy method. Unfortunately, the most common disadvantage of laser therapy is its nonselectivity and requirement of high power density. The use of plasmonic nanoparticles as highly enhanced photoabsorbing agents has thus introduced a much more selective and efficient cancer therapy strategy. In this study, we aimed to demonstrate the selective targeting and destruction of mouth epidermal carcinoma cells (KB cells) using the photothermal therapy of folate-conjugated gold nanorods (F-GNRs). Considering the beneficial characteristics of GNRs and overexpression of the folate receptor by KB cells, we selected F-GNRs as a targeted photothermal therapy agent. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was determined by flow cytometry using an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit. No cell damage or cytotoxicity from the individual treatment of laser light or F-GNRs was observed. However, a 56% cell lethality was achieved for KB cells using combined plasmonic photothermal therapy of 20 μM F-GNRs with seven pulses of laser light and 6-h incubation periods. Cell lethality strongly depends on the concentration of F-GNRs and the incubation period that is mainly due to the induction of apoptosis. This targeted damage is due to the F-GNRs present in the cancer cells strongly absorbing near-infrared laser light and rapidly converting it to heat. This new therapeutic avenue for cancer therapy merits further investigation using in vivo models for application in humans.