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Spinels represent a class of ceramics with promising fundamental properties and a broad spectrum of industrial applications. However, the knowledge of pressure effects on the crystal structure of spinel is limited, which hinders their efficient synthesis using high-pressure techniques. In this paper, the effect of pressure on the crystal structure of mixed spinel ferrite Fe_0.8Ni_1.8Sb_0.4O₄ was investigated at room temperature by in situ synchrotron-based X-ray diffraction and Raman spectroscopy up to 42.19 GPa and 49.51 GPa, respectively. The X-ray diffraction results indicate that Fe_0.8Ni_1.8Sb_0.4O₄ adopts the cubic (spinel-type, space group Fd 3¯ m) structure at ambient conditions, which undergoes a pressure-induced structural transition to a monoclinic phase (space group P2₁/c), commencing at 20.83 GPa. This sluggish structural transformation turns out to be of the first-order accompanied by a volume collapse of about ∼2.2 % when completed at 29.68 GPa. A second phase transition to yet another metastable monoclinic structure with space group C2/m is observed to begin at 33.56 GPa. However, this phase transition does not complete even up to the highest pressure applied in the study. Raman results confirm that Fe_0.8Ni_1.8Sb_0.4O₄ undergoes a pressure-induced phase transition from Fd 3¯ m to P2₁/c at 27.34 GPa. The observed phase transitions are reversible, and their mechanisms are discussed in the light of the Raman spectroscopy data. The present study deepens our understanding of the high-pressure behavior of spinels, which will facilitate their industrial syntheses and a better understanding of their role in planetary interiors.