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Phenol red (PR) is a standard acid-base indicator in cell and tissue culture media, as well as multiple detection protocols. Meanwhile, catalytic nanomaterials such as nanozymes demonstrate great potential in biomedical applications, but there were few studies about the direct impact of nanozymes on the ubiquitous pH indicators. We demonstrate for the first time the degradation of phenol red by highly active nanoceria. The results provide evidence that phenol red is a redox active molecule and it may be oxidized quickly by nanoceria so that its pH-indicating functionality may be lost. Investigators need to be cautious in their routine use of phenol red, particularly when it is exposed to active nanozymes. Herein, we construct a PR-hydrogel as a protective strategy for phenol red against oxidation. Results show that the PR-hydrogel maintained the quantitative acid-base indicating capability while resisting the degradation by nanoceria. The hydrogel exhibits high stability, good pH sensitivity and recyclability, negligible cytotoxicity and dye leaching, which provides a strong practical resolution to the application of phenol red in future challenges of nanomedicines.