Abstract: Hyaluronic acid (HA) was grafted with 1, 12-dodecanediamine and N, N-dimethylacetamide dimethylacetal (DADA), to construct the CO₂ stimuli-responsive HA-ami. In order to investigate its structure, CO₂ stimuli-responsive, cell level as a drug carrier and its tumor targeting, HA-ami was characterized by structure, CO₂ response experimental, cell uptake, cell cytotoxicity, and in vivo tissue distribution. Results indicated that HA-ami was successfully constructed, and had a CO₂ stimuli-responsive. Moreover, HA-ami not only showed the high cellular uptake efficacy and insignificant cytotoxicity, and it was capable of in vivo tumor targeting.