In this study, poly-dopamine functionalized hollow mesoporous silica spheres (PDA/HMSSs) are prepared and exploited as a sensing material for formaldehyde detection in food. The materials were characterized by small-angle X-ray diffraction, scanning electron microscope, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectrometry, and nitrogen adsorption-desorption. The results show that PDA was successfully modified onto the surface of HMSSs. The PDA/HMSSs-based quartz crystal microbalance (QCM) sensors exhibited a low detection limit of 100 ppb, a remarkably rapid response (<5 s), a short recovery (<3 s), as well as excellent sensitivity due to available hollow space and accessibly radial channels. Based on enthalpy change (ΔHo = −51.97 KJ/mol) and the formation of CN bonds, studying on the sensing mechanism revealed that weak chemisorption between PDA/HMSSs and formaldehyde played a significant role in the good specificity and reliability for formaldehyde detection. Furthermore, the as-prepared sensors were directly applied in measuring formaldehyde levels in shiitake mushroom, Chinese cabbage, Litopenaeus vannamei, and broccoli, where rapid detections within 30 s were achieved with high sensitivity, reusability, and good selectivity.