Abstract5‐Aminolevulinic acid (5‐ALA) is one of the most widely used prodrug in clinical photodynamic therapy of dermatological diseases and cancers; yet, its clinical application is still limited by the shallow skin penetration and unsatisfied stability in any existed formulations. Here, 5‐ALA‐loaded hyaluronic acid dissolving microneedles (5‐ALA@HAMNs) are prepared for photodynamic therapy of superficial tumors. The HAMNs can not only assist the loaded 5‐ALA to effectively penetrate the stratum corneum but also provide 5‐ALA with an acidic and oxygen‐free environment to reduce the dimerization of 5‐ALA molecules via Schiff‐base bonds and formation of inactive pyrazine derivatives, thus maintaining its chemical structure and biological activity. The chemical stability of 5‐ALA in HAMNs is confirmed by UV–vis spectra and mass spectra measurements. The 5‐ALA@HAMNs display remarkable tumor elimination both in vitro and in vivo, even after storage at room temperature for nine months, making it a highly potential device for effective delivery of 5‐ALA in cancer photodynamic therapy.