Most melanomas that occur on the skin surface originate from a newly formed nevus and grow outward in a circular pattern and metastasize from the nevus center. Herein, a circular microfabricated substrate is constructed to explore the growth behavior of melanoma cells. Modeling software is used to calculate appropriate parameters, including shape and size, and then the substrates are processed with microfabrication technologies. The results show that the melanoma cells on the circular adhesion substrate are oval and are significant changes in cell spread length, nuclei, area, aspect ratio, Young's modulus, and orientation angles, indicating inhibition of cell polarization. Moreover, three different layers from circular adhesion substrates are selected to construct new substrates, which indicates that the polarization degree of cells is closely related to the number of micropillar arrays on the circular geometric substrate. In addition, flow cytometry demonstrates that the circular substrate reduced the transition from resting/gap 1 phase (G0/G1) to synthesis phase (S phase), thereby decreasing DNA synthesis and proliferation, reminding a potential method for treatment strategy. More importantly, the circular adhesion substrate influences the integrin signaling pathway, which has a potential application and research prospect in the treatment of melanoma.