An efficient artificial light-harvesting system with a two-step sequential energy transfer was fabricated in the aqueous solution based on the host-guest interactions between cyano-substituted p-phenylenevinylene derivative (PPTA) and a water-soluble pillar[5]arene (WP5). PPTA-WP5 complex could self-assemble into nanoparticles, and two fluorescent dyes eosin Y (EY) and Nile Red (NIR) are employed as acceptors to realize sequential energy transfer. The PPTA-WP5-EY-NIR system could achieve efficient two-step sequential energy transfer process from PPTA-WP5 to EY and then to NIR (67% for the first step and 66% for the second step). Moreover, to make full use of the harvested energy, the hydrophobic microenvironment in the assembled nanoparticles is used to promote the aerobic cross-dehydrogenative coupling (CDC) reaction in aqueous medium with 88% yield after 12 h of irradiation. To our knowledge, this is the first example of artificial LHS with two-step energy transfer used to catalyze the CDC reaction in aqueous medium. This work directly mimics the function of photosynthesis in nature of converting solar energy into chemical energy in aqueous solution.