Novel multi-stimuli responsive fluorescence sensors based on amphiphilic copolymers containing hydrophilic N-isopropylmethacrylamide (NIPAM) and AIEgenic tetraphenylethylene-dipicolylamine (TPEDPA) monomers attached to side-chains of copolymers are synthesized. Two copolymers poly(NIPAM)x-co-(TPEDPA)y prepared by free radical polymerization with different molar ratios of monomers NIPAM and TPEDPA (i.e., x:y = 60:1 and 175:1 for P1 and P2, respectively) show good solubilities in organic solvents and water, which exhibit strong cyan fluorescence at 466 nm in aggregation and solid states due to AIE behaviors of TPE units. Upon various external stimuli (temperatures and acid/base conditions), P1 and P2 possess excellent reversible thermo- and pH-responsive fluorescence turn-off/on cyan emissions of TPE units. In addition, with DPA receptor, P1 and P2 are applied as ultrafast, selective and sensitive fluorescence probes for copper ion detection in water based on the TPE fluorescence quenching via photoinduced electron transfer (PET) phenomena, which can be recovered by the addition of disodium ethylenediaminetetraacetate solution. Owing to good water solubilities, amphiphilic copolymers P1 and P2 (containing only 1.6 and 0.6 % molar ratios of AIEgen) exhibit significant sensing towards Cu2+ with very prominent limit of detection values (LOD = 57 and 72 nM, respectively), which are much better than that of hydrophobic monomer TPEDPA (590 nM). Moreover, the fluorescence quenching of TPE units due to PET phenomena is further confirmed by theoretical calculations. Additionally, as an excellent quenching fluorescence sensor with good biocompatibility of P1, its recognition of copper ion and bio-imaging applications in living cells are also reported in this research.