To minimize the toxicity of gold nanoparticles (AuNPs) in cancer treatment, we have developed a technique, which utilizes lesser amount of AuNPs while exhibiting increased treatment efficiency. Rifampicin (RF) is known for its ability to enhance the accumulation of anticancer drugs in multidrug resistant (MDR) cancer cells. In this work we have shown that RF-conjugated AuNPs can greatly enhance the rate as well as efficiency of endocytosis of NPs and hence their concentration inside the cancer cell. Cell viability results showed a remarkable enhancement in the photothermal therapeutic effect of Au nanorods in presence of RF. This is expected to decrease the demand on the overall amount of AuNPs needed for treating cancer and thus decreasing its toxicity.