Natural sepiolite powders were modified and refined using a mechanochemical wet modification process, and one-dimensional sepiolite powders were prepared and stably dispersed in the lubricating oil. An orthogonal experimental method of 4-factors and 3-levels is applied to investigate the effect of load, reciprocating frequency, sliding duration and content on tribological behaviors of sepiolite as additives in 500SN mineral base oil using a reciprocating sliding wear tester. The morphology, microstructure, chemical composition and state, and micromechanical properties of the worn surfaces were analyzed using scanning electron microscopy (SEM), focused ion beam (FIB) and transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and nanoindentation tester. The lubrication and friction-reduction mechanisms of the sepiolite additives are discussed in detail. The results indicate that the order of factors affecting the friction-reducing performance of sepiolite additives can be given as: sepiolite content, sliding duration, applied load and reciprocating frequency. On the other hand, the influence of the factors on the anti-wear property is: reciprocating frequency > sepiolite content > sliding duration > applied load. A tribolayer consisting of metal oxides, ceramic particles, graphite and organics is formed on the worn surface, which is conducive to the excellent tribological behavior of sepiolite due to its excellent lubricity, high hardness and low elastic modulus. The formation of the tribolayer is closely related to the unique physicochemical properties of the one-dimensional mineral clay and tribological conditions.