<p>Skeletal muscle has an innate ability to restore damaged muscle fibers by contributing specific progenitor cells, called muscle satellite cells. Here we show that secretoglobin (SCGB) 3A1, a tumor suppressor gene in various malignancies including rhabdomyosarcoma, is induced just after muscle injury and contributes to damaged muscle fiber regeneration. Lineage tracing of SCGB3A1 in mice show that SCGB3A1-positive cells highly express myosin heavy chain (MyHC)-IIX in damaged fiber area. <i>Scgb3a1</i>-null and <i>Pax7</i>^{<i>CreERT2</i>};<i>Scgb3a1</i>^<i>f/f</i> conditional-null mice exhibit defective IIX and IIB fiber regeneration, with a concomitant reduction in the expression of <i>Notch3</i>, a gene important for the maintenance of satellite cell self-renewal pools. Aged <i>Scgb3a1</i>-null mice show reduced size of muscle fibers and mass, resulting in compromised muscle performance as compared to the age-matched wild-type mice. This study reveals that SCGB3A1 is an unexpected novel molecule expressed in muscle satellite cells that contributes to fiber type specific muscle regeneration.</p>