Studies have shown that many complex diseases are sex-determined. When conducting genetic association studies on Xchromosome, there are two important epigenetic factors which should be considered simultaneously: X-chromosome inactivation and genomic imprinting. Currently, there have been several association tests accounting for the information on X-chromosome inactivation. However, these tests do not take the imprinting effects into account. In this paper, we propose a novel association test simultaneously incorporating X-chromosome inactivation and imprinting effects based on case–parent trios and control–parent trios for female offspring and case–control data for male offspring, denoted by MLR_XCII. Extensive simulation studies are carried out to investigate the type I error rate and the test power of the proposed MLR_XCII . Simulation results demonstrate that the proposed test controls the type I error rate well andis more powerful than the existing method when imprinting effects exist. The proposed MLR_XCII test is valid and powerful in genetic association studies on X-chromosome for qualitative traits and thus is recommended in practice.