Stimuli response or controlled release is a new research hotspot in nanomedicine; however, there is scarce research on organic nanomedicines with stimuli responses, which limits their practical biological applications. In addition, homoharringtonine (HHT) has been used as an effective anticancer agent, but reducing its toxicity and side effects is an urgent problem to be solved. Herein, an EGFR (epidermal growth factor receptor) aptamer-modified HHT-loaded PLGA-SS-PEG nanomedicine was developed. The nanomaterial possesses spherical morphology and admirable biocompatibility. After targeted endocytosis in tumour cells via the selective recognition between EGFR and its aptamer, the PLGA nanomedicine is triggered by a high GSH level and releases its cargo in lung cancer cells. The in vitro and in vivo results reveal that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells, but also possessed better therapeutic efficacy and less toxic side effects compared with the free anticancer agent. Consequently, this study provides a novel approach to construct a biodegradable nanomedicine with targeted recognition and stimuli response. Moreover, it inhibited the proliferation of lung cancer cells with high efficiency and low toxicity. Importantly, the PLGA nanomedicine demonstrates encouraging potential as a multifunctional nano-system applicable for cancer therapy.