A pH-stimuli amphiphilic lignin-based copolymer was prepared, and it could self-assemble to form spherical nanomicelles with the addition of “switching” water. The morphology, structure, and physical properties of micelles were characterized with transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), particle-size analysis, and zeta-potential measurement. In vitro drug release exemplified that the micelles were pH-sensitive, retaining more than 84.36% ibuprofen (IBU) in simulated gastric fluid (pH 1.5) and presenting a smooth release of 81.81% IBU in simulated intestinal fluid (pH 7.4) within 72 h. Cell culture studies showed that the nanomicelles were biocompatible and boosted the proliferation of human bone marrow stromal cells hBMSC and mouse embryonic fibroblast cells NIH-3T3. Interestingly, the nanomicelles inhibited the survival of human colon cancer cells HT-29 with a final survival rate of only 5.34%. Therefore, this work suggests a novel strategy to synthesize intelligent lignin-based nanomicelles that show a great potential as oral drug carriers.