The cubic PbS nanoflowers were successfully synthesized by the biomolecule-assisted method in the presence of supercritical carbon dioxide. This is an effective, simple and green synthetic method for the preparation of nanomaterials. It is noteworthy that the dosage of cetyltrimethylammonium bromide (CTAB) and chitosan as well as appropriate reaction time and pressure of system are crucial to form the unusual nanoflower structured PbS. The unique nanoflowers have numerous petals, which grow along the < 100 > direction as a single crystal. Especially, the nanoflower PbS indicates better sensitivity to the laser power via Raman spectra. Although the product size of PbS obtained is larger than the Bohr radius, its UV-vis absorption spectrum shows a remarkable blue-shift from that of bulk PbS due to quantum-confinement effects.