Biocompatible, multifunctional, stimuli responsive, and high drug loading capacity are key factors for the new generation of drug delivery platforms. However, it is extremely challenging to create such a platform that inherits all these advanced properties in a single carrier. Herein, porous silicon nanoparticles (PSi NPs) and giant liposomes are assembled on a microfluidic chip as an advanced nano-in-micro platform (PSi NPs@giant liposomes), which can co-load and co-deliver hydrophilic and hydrophobic drugs combined with synthesized DNA nanostructures, short gold nanorods, and magnetic nanoparticles. The PSi NPs@giant liposomes with photothermal and magnetic responsiveness show good biocompatibility, high loading capacity, and controllable release. The hydrophilic thermal oxidized PSi NPs encapsulate hydrophobic therapeutics within the hydrophilic core of the giant liposomes, endowing high therapeutics loading capacity with tuneable ratio and controllable release. It is demonstrated that the DAO-E A B? DNA nanostructures have synergism with drugs and importantly they contribute to the significant enhancement of cell death to doxorubicin-resistant MCF-7/DOX cells, overcoming the multidrug resistance in the cancer cells. Therefore, the PSi NPs@giant liposomes nano-in-micro platform hold great potential for a cocktail delivery of drugs and DNA nanostructures for effective cancer therapy, controllable drug release with tuneable therapeutics ratio, and both photothermal and magnetic dual responsiveness.