Deep-sea tube box is a crucial and basic structural component of various deep-sea equipment such as deep-sea submarine and unmanned underwater vehicles. The deep-sea ultra large unmanned underwater vehicle (ULUUV) is the most representative one of them. Tube boxes are the basic modular members on the ULUUV, which are widely used as the load-bearing hull in torpedo launch, load transportation, pipeline protection and etc. Due to the extremely harsh operation condition, deep-sea tube box simultaneously suffers extremely high lateral water pressure and tremendous axial compression induced by water pressure. Considering the strict requirements for lightweight, high strength, and corrosion resistance of deep-sea tube boxes, carbon fiber-reinforced polymers (CFRP) have become the most potential choice for the construction materials of future deep-sea tube box. Thus, the aim of this paper is to make a structure design of a deep-sea CFRP tube box which can operate at the water depth of 5000 ft. In this paper, a detailed design process of the deep-sea CFRP tube box was introduced, including geometrical configuration, critical buckling load prediction method, FE modeling technique and experimental validation. Corresponding to 5 ply schemes, 495 cases of FE analyses were performed to obtain the ultimate strength envelopes of the CFRP tube box subjected to combined axial compression and external lateral water pressure. Based on the obtained results, the best ply scheme for the deep-sea CFRP tube box was figured out. This paper could provide design method and data references for deep-sea CFRP structures which are subjected to combined loads.