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Background: Primary insomnia (PI) is defined as a sleep disorder with no definite cause or inducement. Electroacupuncture, a treatment of inserting needles into specific points on the body surface and applying electrical stimulation, has been proved effective in treating PI with minimal adverse effects. However, the influence of gender difference on the clinical treatment efficacy of electroacupuncture for PI patients remains unclear. Therefore, we designed a clinical trial to compare the clinical treatment efficacy of electroacupuncture for PI patients with different genders. The research on the mechanism of electroacupuncture suggested it could modulate the sleep and wakefulness by activating or deactivating brain regions via a needling/tactile somatosensory specific stimulus. Therefore, we also designed a resting‐state functional magnetic resonance imaging (rs‐fMRI) study to detect the spontaneous brain activity of PI patients before and after the electroacupuncture treatment. Method: Thirty PI patients were recruited to accept 5‐week electroacupuncture treatment on HT‐7. Athens Insomnia Scale (AIS) and Pittsburgh sleep quality index (PSQI) questionnaires were used to evaluate the clinical treatment efficacy. Rs‐fMRI was employed to observe the spontaneous brain activity in the resting state at the baseline and after 5 weeks of electroacupuncture treatment, which was measured by the fractional amplitude of low‐frequency fluctuations (fALFF). Result: The AIS and PSQI scores were significantly decreased both in the female PI group and the male PI group after treatment. The decreased PSQI of female patients was significantly more than that of male patients (p <.05). The gender‐related difference in the cerebral response to electroacupuncture was mainly in posterior cingulate and supramarginal gyrus. Conclusion: There is a gender‐related difference in the clinical treatment efficacy of electroacupuncture for PI patients, and female patients may benefit more from electroacupuncture. Gender‐related differences in the cerebral response to electroacupuncture may be one of the factors affecting clinical treatment efficacy. [ABSTRACT FROM AUTHOR]