Lithium-ion batteries are key elements of electric vehicles and energy storage systems, and their accurate State of Charge (SOC) estimation is momentous for battery energy management, safe operation, and extended service life. In this paper, the Multi-Kernel Relevance Vector Machine (MKRVM) and Whale Optimization Algorithm (WOA) are used to estimate the SOC of lithium-ion batteries under different operating conditions. In order to better learn and estimate the battery SOC, MKRVM is used to establish a model to estimate lithium-ion battery SOC. WOA is used to automatically adjust and optimize weights and kernel parameters of MKRVM to improve estimation accuracy. The proposed model is validated with three lithium-ion batteries under different operating conditions. In contrast to other optimization algorithms, WOA has a better optimization effect and can estimate the SOC more accurately. In contrast to the single kernel function, the proposed multi-kernel function greatly improves the precision of the SOC estimation model. In contrast to the traditional method, the WOA-MKRVM has a higher precision of SOC estimation.