Senescence is a leading cause of age-related cataract (ARC). The current study indicated that the senescence-associated protein, p53, total laminin (LM), LM alpha 4, and transforming growth factor-betal (TGF-beta 1) in the cataractous anterior lens capsules (ALCs) increase with the grades of ARC. In cataractous ALCs, patient age, total LM, LM alpha 4, TGF-beta 1, were all positively correlated with p53. In lens epithelial cell (HLE B-3) senescence models, matrix metalloproteinase-9 (MMP-9) alleviated senescence by decreasing the expression of total LM and LM alpha 4; TGF-beta 1 induced senescence by increasing the expression of total LM and LM alpha 4. Furthermore, MMP-9 silencing increased p-p38 and LM alpha 4 expression; anti-LM alpha 4 globular domain antibody alleviated senescence by decreasing the expression of p-p38 and LM alpha 4; pharmacological inhibition of p38 MAPK signaling alleviated senescence by decreasing the expression of LM alpha 4. Finally, in cataractous ALCs, positive correlations were found between LM alpha 4 and total LM, as well as between LM alpha 4 and TGF-beta 1. Taken together, our results implied that the elevated LM alpha 4, which was possibly caused by the decreased MMP-9, increased TGF-beta 1 and activated p38 MAPK signaling during senescence, leading to the development of ARC. LM alpha 4 and its regulatory factors show potential as targets for drug development for prevention and treatment of ARC.