p120-catenin (p120) has been shown to be essential for cadherin stability. Here, we show that p120 is capable of regulating microtubule (MT) dynamics in a cadherin-independent manner. When p120 was depleted in cadherin-deficient Neuro-2a (N2a) cells, MT stability was reduced, as assessed by the nocodazole sensitivity of MTs. On the contrary, over-expression of p120 caused MTs to become resistant to nocodazole. Time-lapse recording of GFP-tagged EB1, a protein which binds the growing plus-ends of MTs, introduced into these cells demonstrated that the plus ends underwent more frequent catastrophe in p120-depleted cells. In addition, p120 knockdown up-regulated the motility of isolated cells, whereas it down-regulated the directional migration of cells from wound edges; and these migratory behaviors of cells were mimicked by nocodazole-induced MT depolymerization. These results suggest that p120 has the ability to regulate MT dynamics and that this activity, in turn, affects cell motility independently of the cadherin adhesion system.