Noninvasive near infrared light responsive cancer treatment is a promising modality, however some inherent drawbacks of conventional phototherapy heavily restrict their application in clinic. Rather than producing heat or reactive oxygen species, here we developed a multifunctional yolk-shell nanoplatforms could generate plenty of microbubbles upon laser irradiation. The bubbles are able to kill cancer cells due to mechanical effect and the damage is efficiently amplified by small interference RNA (siRNA) which is absorbed on the surface of nanoparticles. In vitro experiments demonstrate this nanoplatform exhibits almost the same transfer efficiency of siRNA comparing with commercial transfection agents and possesses excellent bubble-production ability. The results of cellular toxicity test verify the siRNA improve the damage to cancer cells caused by gasification process upon NIR laser exposure. After surface modification, the yolk-shell nanoparticles could target cancer cells selectively. Guided by photoacoustic and ultrasonic imaging, these results are confirmed in a humaized orthotropic lung cancer model. The yolk-shell nanoplatforms demonstrate outstanding tumor regression with few side effect under a relatively low laser power density. Therefore, the multifunctional nanoparticles that combining bubble-induced mechanical effect with RNA interference are expected to be an effective NIR light responsive oncotherapy.