The development of heterogeneous molecule-based catalysts for red light-mediated photocatalysis is still challenging due to the improper light absorption for most materials and the photoactivity deactivation for solid assembly. Herein, red light photocatalysis with a hydrogen-bonded organic framework (HOF) is established. This HOF, named HOF-66, is formed from the self-assembly of guanine-decorated naphthalenediimide (NDI) molecule through hydrogen-bonded guanine-quadruplex nodes, showing square grid supramolecular layers confirmed by powder X-ray diffraction analysis. In contrast to unsubstituted NDI HOF, introduction of ethylamino groups to NDI core in HOF-66 tunes strong electronic maximum absorption peak to 619 nm, allowing red light photocatalysis of singlet oxygen evolution proved by 1,3-diphenylisobenzofuran degradation and electron spin resonance determination. Particularly, under the same conditions, the sulfide oxidation rate in the presence of HOF-66 was 28 times higher compared to its unsubstituted analogue. This work integrates the molecular design and aggregation effect towards the application of HOFs, opening a new gate for red light photocatalysts.