Objective: Cell migration requires coordination of mechanical forces generated in different regions of the cell. Fine-tuned cytosolic Ca²⁺ signals are linked to mechano-signalling. To date, the source of these Ca²⁺ signals is unknown. It is discussed controversially whether TRP channels could be involved. Here, we investigated the integration of TRPC1 channels in mechanotransduction during cell migration. Methods: To study TRPC1 function we used TRPC1-/- fibroblasts or silenced TRPC1 by siRNA in MDCK-F cells. Cell migration was analyzed by time-lapse video microscopy and combined with intracellular Ca²⁺ measurements. Results: TRPC1-/- fibroblasts and TRPC1 knockdown cells have largely increased cell areas pointing to a defect in cell volume regulation. We tested the connection of mechanotransduction and TRPC1 activity during migration by analyzing cell motility on matrices with variable stiffness (5, 10 and 15 kPa). Only TRPC1 expressing cells respond differentially. Furthermore, we applied a biaxial stretch stimulus during migration via a flexible silicone matrix. After 0.4% stretch, TRPC1 expressing cells show Ca²⁺ transients and migrate in parallel to the direction of the mechanical stimulus. In contrast, migration of TRPC1 knockdown cells is unaffected by mechanical stretch. Conclusion: Our data indicate that TRPC1 is linked to mechano-signalling during cell migration.