The correct function of neurons depends on their structural integrity, as well as that of their long processes, the axon and dendrites. In C. elegans, the posterior lateral mechanosensory neuron (PLM), is ensheathed within the epidermis and detects gentle touch. We have previously demonstrated that correct neuron-epidermal attachment is critical to protect these sensory neurons from degeneration caused by the mechanical strain of body movement. The full complement of adhesion proteins and extracellular matrix molecules that function at these attachment sites remains to be elucidated and the cellular and molecular pathways that mediate this protection are unknown. To fill this knowledge gap, we conducted an unbiased forward genetic screen and identified novel mutations in two genes. The first, lam-2/laminin-γ, is associated with the integrin adhesion complex and the second, pat-4/ILK, is a component of the integrin adhesion complex. Both LAM-2 and PAT-4 are required to maintain PLM axon integrity. lam-2; pat-4 double mutants present with significantly increased rates of PLM axonal breakage compared to wild type animals. Endogenous expression of wild-type lam-2 and pat-4 can fully rescue axonal breakages. We show that PAT-4 functions in both the epidermis and the PLM neuron, to protect the PLM axon from damage. Using a novel split-GFP strategy to visualize these molecules exclusively at the interface of neurons and epithelia, we show LAM-2 localizes in a punctate pattern adjacent to the PLM axon, while PAT-4 localizes to discrete regions adjacent to sensory axons in the skin. Consistent with the notion that LAM-2/laminin-γ and PAT-4/ILK regulate integrin adhesion complexes, directly modulating integrin adhesion by targeting integrin heterodimer formation resulted in the same PLM axonal breakage phenotype observed in lam-2; pat-4 double mutants. Taken together, our data supports a model in which LAM-2/laminin-γ and PAT-4/ILK function synergistically to protect axons by regulating integrin adhesion between the epidermis and sensory neurons.