Myoblasts migration is a key step in myogenesis. It allows myoblasts alignment and fusion into myotubes. This process has been shown to involve m- or m-calpains, two calcium-dependent cysteine proteases. Indeed, growth factor-induced migration is accompanied by an increase of calpains expression and the rate of migration is reduced in transfected cells overexpressing calpastatin, an endogenous inhibitor of calpains. In the present paper, we measured calpain activity in situ (fluorimetric measurements) and show, for the first time, a peak of activity at the beginning of the differentiation process. Besides, we recently reported that, in adult skeletal muscle fibres, calpains were specifically activated by a store operated entry of calcium. In the present study, we therefore repressed the expression of TRPC1 in myoblasts and studied its influence on differentiation. Expression of TRPC1 was reduced by 60 to 80 % in myoblasts expressing a shRNA anti-TRPC1 in comparison to myoblasts expressing a control shRNA. These cells presented a largely reduced store-operated entry of calcium. Differentiation was induced by replacing foetal calf serum 10% by horse serum 1% in  50% confluent cell cultures. In these conditions, fusion of myoblasts into myotubes was significantly slowed down in TRPC1 knock-down myoblasts. We observed that this reduction of fusion was due to an absence of alignment of myoblasts. This observation was corroborated by the fact that myoblasts tranfected with shRNA anti-TRPC1 also presented a significantly reduced speed of migration after wounding. This effect could be mimicked by applying 2 to 5 mM GsMTx4 toxin, an inhibitor of TRPC1. In parallel, we found that the peak of calpain activity observed at the beginning of differentiation was abolished in cells repressing TRPC1. We therefore suggest that an entry of calcium through TRPC1 channel induces a transient activation of calpains, allowing in its turn, myoblasts migration and fusion.