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• Flammability characteristics of R1216 mixed with R32 and R152a were investigated. • The suppression effect of R1216, R134a, R1233zd(E), and R13I1 was compared. • The flame inhibition mechanism of R1216 was analyzed. R1216 (1,1,2,3,3,3-hexafluoro-1-propene), which has a low global warming potential, is regarded as the new generation of environmentally friendly working fluid in ORCs (organic Rankine cycle) and refrigeration systems. Besides, it also has the advantage of nonflammable property. Thus, R1216 can be mixed with some flammable working fluids to develop new mixed alternatives, which can possess a combination of chemical, environmental, thermodynamic, and safety properties. In this work, the flammability limits of R1216/R32 and R1216/R152a were measured in a 12L spherical glass vessel according to the method of ASTM E681. And the critical flammable volumetric ratios of R1216 on R32 and R152a were about 0.15 and 1.1, respectively. This study also found that the ratio of F atoms to H atoms for the two mixtures had a close relationship with the flammability limit ranges. Finally, the flame inhibition performances of R1216 were compared with other commonly used flame retardants, such as R134a, R13I1 (trifluoroiodomethane), and R1233zd(E) (trans -1-Chloro-3,3,3-trifluoro-propene). It can be concluded that the rank of the inhibition effects was R1216 > R13I1 > R134a > R1233zd(E). And a flame retardant, which contained a higher F/H ratio and much more Cl, I, and CF 3 radicals, can possess a higher flammability inhibition efficiency. [ABSTRACT FROM AUTHOR]