Raman spectra were acquired from the synthetic cubic K6Fe25S26Cl phase (55.3 wt% Fe) and ten natural djerfisherites K6(Fe,Cu,Ni)25S26Cl with various contents of Fe (from 15.5 to 22.6 atoms per formula unit (apfu)) and Ni + Cu + Co (from 1.4 to 9.0 apfu). The natural samples came from rocks of the Udachnaya, Obnazhennaya and Vtorogodnitsa kimberlite pipes and high-grade contact marbles near Kochumdek River (Siberian craton, Russia). Diagnostic features of both synthetic and natural djerfisherite Raman spectra can be summarized as follows: the presence of two strong bands at 264–273 and 321–344 cm−1 and from two to five medium/weak bands in the region from 90 to 190 cm−1. Raman spectra of Fe-rich ((Ni + Cu + Co) < 2.4 apfu) djerfisherite have up to nine bands, whereas the number of Raman bands in spectra of djerfisherite with high impurity concentration ((Ni + Cu + Co) = 8.7–9 apfu) reduces to four. The Raman spectra of djerfisherite enriched in impurities ((Ni + Cu + Co) = 5–9 apfu) are also characterized by broadening and asymmetry of bands in comparison with Ni + Cu + Co-poor djerfisherite. Experimental Raman spectra of synthetic and natural djerfisherites show good agreement with theoretical spectra calculated using lattice-dynamical software. The group of bands in the range 90–190 cm−1 is associated with the S–Fe–S bending vibrations in FeS4 tetrahedra and FeS6 octahedra. The band group in the range of 260–350 cm−1 is due to the Fe–S stretching vibrations in both polyhedra.