In this paper, a 16-channel analog front-end (AFE) ECoG-signal acquisition circuit for closed-loop seizure control system is presented. It is composed of 16 auto-reset chopper-stabilized capacitive-coupled instrumentation amplifiers (AR-CSCCIA) with band-pass filters, 16 programmable transconductance-gain amplifiers, a multiplexer, a transimpedance amplifier, and a 10-bit SAR ADC. The low input-referred noise is achieved by using chopper modulation technique in AR-CSCCIA. To reduce the undesired effects of chopper modulation, an improved offset reduction loop (ORL) is proposed to reduce output offset generated by input chopper mismatches. The digital ripple reduction loop (RRL) is also used to reduce chopper ripple. Moreover, to prevent from overstress in MOS devices caused by high stimulation voltage, an input protection circuit with high-voltage-tolerant switches is proposed to make the AFE amplifiers sharing the same electrode with high voltage stimulators. The fabricated AFE acquisition circuit has 49.1/59.1/67.9 dB programmable gain and 2.09uVrms input referred noise in a bandwidth 0.5-100 Hz. The measured power consumption of AFE is 3.26 uW per channel and the noise efficiency factor (NEF) is 3.78.