The γ-cyclodextrin-based metal–organic framework (γ-CD-MOF) composite was designed and prepared toward targeted anticancer drug delivery and cancer therapy. Large amounts of graphene quantum dots (GQDs) were embedded in the γ-CD-MOF matrix (denoted as GQDs@γ-CD-MOF) to endow the γ-CD-MOF with strong fluorescence, which was then modified by pH responsive poly(ethyleneglycol)dimethacrylate (PEGMA) through surface initiated atom transfer radical polymerization (SI-ATRP) to fabricate the PEGMA@GQDs@γ-CD-MOF composite. Then, the cancer cell-targeted probe was obtained by immobilizing the AS1411 aptamer over it (denoted as AS1411@PEGMA@GQDs@γ-CD-MOF) and it exhibits pH-responsive release function and excellent targeting ability. Large amounts of antitumour drug, doxorubicin hydrochloride (DOX), could be encapsulated within this composite due to the chemical-rich functionality, and the resultant pH-responsive DOX delivery system (denoted as DOX/AS1411@PEGMA@GQDs@γ-CD-MOF) displayed a higher DOX loading of 89.1% with sustained release than the pristine γ-CD-MOF and GQDs@γ-CD-MOF. The targeting specificity investigation revealed that this DOX delivery system was effectively internalized via receptor mediated endocytosis with high selectivity. The in vivo antitumour study with tumour-bearing mice illustrated that the tumour growth can be effectively suppressed and partially ablated with negligible side effects after treatments. Therefore, the proposed AS1411@PEGMA@GQD@γ-CD-MOF composite is promising for effective DOX delivery and tumour growth inhibition both in vitro and in vivo, showing great potential for anticancer therapy.