This study was to investigate optimized extraction conditions for Chlorella sorokiniana (C. sorokiniana) water extracts with antioxidant functionality and potential key compounds involved. A 2-factor, 5-level response surface methodology was employed using extraction temperature (40-100°C) and time (0.5-6h) as factors. It is indicated that, among the C. sorokiniana extracts examined, the maximal value in yield was 18.0% (w/w) on biomass basis; in 75% ethanol solubility of water extract (WS-E75S%, the potentially major antioxidant fraction), 38.0% (w/w) on extract basis; in total phenolic content (TPC), 3.17 GAEmg/g on extract basis. The highest antioxidant activities were shown by a 50% DPPH scavenging concentration (SC50)=7.36mg/ mL, 50% Fe2+ chelating concentration (CC50,)=10.4mg/mL, and reducing power increment per unit concentration=0.044mL/mg. By statistical analysis with RSREG program, the obtained polynomials for yield, WS-E75S%, SC50 and CC50 as a function of temperature and time could explain 78.9-82.2% of data variations. An optimal extraction condition was concluded at 100°C for 1h, to give high values in all yield, WS-E75S%, and antioxidant activities (i.e. low SC50 and CC50 values). In WS-E75S, the major compositions were likely nucleic acids and their analogues with ethylene structure, accompanying with detectable amounts of possibly polyunsaturated fatty acids, fatty alcohols, or phytols with acyl dienes, buta-1, 3-diene or ethylene structure. Besides these Phytochemicals, the water extract contained carbohydrates of mainly glucose and ribose (52.4 and 25.9mol%, respectively), followed by galactose and rhamnose, and two molecular fractions. Conclusively, Chlorella water extract at optimally 100 °C for 1h could yield~18% (w/w), contain WS-E75S~37% (w/w) and have statistically predicted SC50 ~3.0mg/mL and CC50 ~11mg/mL.