In this paper, a 16-channel analog front-end (AFE) electrocorticography signal acquisition circuit for a closed-loop seizure control system is presented. It is composed of 16 input protection circuits, 16 auto-reset chopper-stabilized capacitive-coupled instrumentation amplifiers (AR-CSCCIA) with bandpass filters, 16 programmable transconductance gain amplifiers, a multiplexer, a transimpedance amplifier, and a 128-kS/s 10-bit delta-modulated successive-approximation-register analog-to-digital converter (SAR ADC). In closed-loop seizure control system applications, the stimulator shares the same electrode with the AFE amplifier for effective suppression of epileptic seizures. To prevent from overstress in MOS devices caused by high stimulation voltage, an input protection circuit with a high-voltage-tolerant switch is proposed for the AFE amplifier. Moreover, low input-referred noise is achieved by using the chopper modulation technique in the AR-CSCCIA. To reduce the undesired effects of chopper modulation, an improved offset reduction loop is proposed to reduce the output offset generated by input chopper mismatches. The digital ripple reduction loop is also used to reduce the chopper ripple. The fabricated AFE amplifier has 49.1-/59.4-/67.9-dB programmable gain and 2.02-μVrms input referred noise in a bandwidth of 0.59-117 Hz. The measured power consumption of the AFE amplifier is 3.26 μW per channel, and the noise efficiency factor is 3.36. The in vivo animal test has been successfully performed to verify the functions. It is shown that the proposed AFE acquisition circuit is suitable for implantable closed-loop seizure control systems.