Abstract: During wound healing, the moisture level within the wound microenvironment serves as a key indicator of the healing status, making its real-time monitoring crucial for preventing infection and inflammation. To achieve stable monitoring of wound humidity, a surface acoustic wave (SAW) humidity sensor based on copper oxide (CuO) nanowires was designed. To ensure compatibility with the weakly acidic wound microenvironment, the CuO nanowires were functionalized with a self-assembled hydrophobic fluorination layer, which effectively shields them from H⁺ corrosion, thereby markedly enhancing the sensor's environmental stability. Experiments demonstrate that this sensor exhibits a sensitivity of 2.42 kHz/%RH in high-humidity ranges, along with excellent repeatability and stability exceeding 14 days. After 8 hours of immersion in a pH=4 acidic buffer solution, the sensor’s performance degraded by only 0.94%, showcasing outstanding corrosion resistance. This study provides a reliable sensing solution for real-time monitoring of wound inflammation and offers technical support for the application of surface acoustic wave sensors in biomedical detection.