Purpose. To determine whether class 1 UV-blocking contact lenses protect against UVB radiation-induced damage in a human lens epithelial cell line (HLE B-3) and postmortem human lenses using a proteomics approach. Methods. HLE B-3 cells were exposed to 6.4 mW/cm 2 UVB radiation at 302 nm for 2 minutes (768 mJ/cm 2) with or without covering by senofilcon A class 1 UV-blocking contact lenses or lotrafilcon A non-UV-blocking (lotrafilcon A has some UV-blocking ability, albeit minimal) contact lenses. Control cells were not exposed to UVB radiation. Four hours after treatment, cells were analyzed by two-dimensional difference gel electrophoresis and tandem mass spectrometry, and changes in protein abundance were quantified. F-actin and microtubule cytoskeletons were examined by fluorescence staining. In addition, human donor lenses were exposed to UVB radiation at 302 nm for 4 minutes (1536 mJ/cm 2). Cortical and epithelial cell proteins were scraped from lens surfaces and subjected to the same protein analyses. Results. Senofilcon A lenses were beneficial for protecting HLE B-3 cells against UVB radiation-induced changes in caldesmon 1 isoform, lamin A/C transcript variant 1, DEAD (Asp-Glu-Ala-Asp) box polypeptide, β-actin, glyceraldehyde 3-phosphate dehydrogenase (G3PDH), annexin A2, triose phosphate isomerase, and ubiquitin B precursor. These contact lenses also prevented actin and microtubule cytoskeleton changes typically induced by UVB radiation. Conversely, non-UV-blocking contact lenses were not protective. UVB-irradiated human lenses showed marked reductions in αA-crystallin, αB-crystallin, aldehyde dehydrogenase 1, βS-crystallin, βB2-crystallin, and G3PDH, and UV-absorbing contact lenses significantly prevented these alterations. Conclusions. Senofilcon A class 1 UV-blocking contact lenses largely prevented UVB-induced changes in protein abundance in lens epithelial cells and in human lenses.