With the rapid development of the electronics industry, the power of devices continues to rise, and seeking more efficient cooling technologies has become a key challenge in various applied scenarios. This study contributes to a novel and efficient heat dissipation method for chips employing liquid metal as a coolant. In this paper, the flow and heat transfer performance of a novel liquid metal (Ga61In25Sn13Zn1) in a mini-channel heat sink is conducted. Using pressure difference, pump power, and total thermal resistance as object parameters, a comprehensive optimization about Hp (channel height), Wc (channel width), Ww (wall thickness), and tb (base thickness) is presented. The optimized parameter combination is Hp = 7 mm, Wc = 0.6 mm, Ww = 0.4 mm, and tb = 0.2 mm. Furthermore, all of the optimization parameters are verified through the design method of orthogonal experiments.