Lung disease is a leading cause of morbidity and mortality worldwide. Innate immune responses in the lung play a central role in the pathogenesis of lung disease and the maintenance of lung health, and thus it is crucial to understand factors that regulate them. Hyaluronan is ubiquitous in the lung, and its expression is increased following lung injury and in disease states. Furthermore, hyaladherins like inter-α-inhibitor, tumor necrosis factor-stimulated gene 6, pentraxin 3 and versican are also induced and help form a dynamic hyaluronan matrix in injured lung. This review synthesizes present knowledge about the interactions of hyaluronan and its associated hyaladherins with the lung immune system, and the implications of these interactions for lung biology and disease. •Hyaluronan and hyaladherins (IαI, TSG-6, PTX3, versican) are highly expressed in lung tissue and respond dynamically to lung injury•Hyaluronan and its hyaladherins activate and modulate the lung innate immune system in response to injury•Hyaluronan-innate immune interactions in lung injury are highly variable, suggesting that the hyaluronan matrix is a major regulator of lung innate immunity.