The modern medicine requires precise diagnostic techniques while the fluorescent imaging shows great potential in such applications due to its excellent sensitivity and high resolution.However,conducting fluorescent imaging in deep-tissue is not so easy because most luminogens show short-wavelength excitation,which may undergo severe light scattering by the bio-tissue.The marriage of fluorescent imaging with nonlinear optical(NLO)effect can alleviate such adverse effects by utilizing NIR laser to reduce light scattering.On the other hand,scientists are enthusiastic in pur-suing luminescent materials,which can match well with NLO appli-cation.Aggregation-induced emission(AIE)materials exhibit huge advantages in such aspect not only because of its high luminescent efficiency in aggregate state but also due to its excellent photo-stability(a key factor to meet laser application because of its ultra-high energy density).Inspired by this,many interesting and mea-ningful works have sprung up based on AIE luminogens with NLO effect in recent years,and for such reason,it motivates us to summarize them to give a systematic presentation.Here,we first give a brief introduction of the principle of NLO effect.Secondly,the strategies for improving the NLO effect of AIE materials,such as increasing molecular conjugation,introduction of donor-acceptor effect,induction of centrally asymmetric array of AIE molecules in crystals and introduction of intermolecular interactions are clarified.In the final part,we also present the multiple applications of AIEgens with NLO effect in cell imaging,deep-tissue tumor and brain blood vessel imaging and photodynamic therapy.We believe,with this review,the topic will attract more attention from the scientists in multi-science field to accelerate the development of AIE materials in biomedical applications.