TME, including that of head and neck squamous cell carcinoma (HNSCC), is typically weakly acidic, with a pH range of 6.4 to 7.0.[7] pHLIPs represent a class of peptide molecules that undergo structural and functional changes in response to environmental pH alterations, enabling their insertion into cell membranes under acidic conditions.[8] To evaluate the insertion efficiency of preS1‐pHLIP into tumor cell membranes under acidic conditions, we treated PreS1‐pHLIP nanomicelles with MMP2 and assessed membrane anchoring in the SCC7 mouse squamous cell carcinoma cell line. The gene discussed is MMP2; the disease is neoplasm.