In-vivo animal tests were performed to investigate the feasibility of photothermal therapy based on porous silicon nanoparticles (PSiNPs) in combination with a near-infrared (NIR) laser. The in-vivo animal test results showed that the murine colon carcinoma (CT-26) tumors were completely resorbed with minimal damage to surrounding healthy tissue within 5 days after PSiNPs and NIR laser treatments. In contrast, tumors in the groups treated only with PSiNPs or NIR and a control group continued to grow until the mice died. All of the mice treated with both PSiNPs and NIR remained healthy and free of tumors even 90 days after the treatment. In-vivo fluorescence imaging and the urine and feces tests revealed that PSiNPs injected intratumorally into mice were cleared mainly through the urine. The in-vivo animal test results suggest that thermotherapy based on porous silicon in combination with NIR laser irradiation can efficiently destroy cancer cells selectively without damaging the surrounding healthy cells.