Changes in the structural parameters of trigonal honeycomb layers of Mn3NiTa2O9 are reported under pressures up to 14 GPa by in situ synchrotron x-ray diffraction employing a diamond anvil cell with a 4:1 methanol–ethanol mixture as the pressure transmitting medium (PTM). The lattice parameters a, c, the ratio c/a, and the volume V of the unit cell all decrease almost linearly with an increase in pressure P up to a critical pressure PC = 9.2 GPa. The fit of the V vs P data for P < PC to the expression for the equation of state yields the bulk modulus = 144.5 GPa for the trigonal Mn3NiTa2O9. For P > PC, the widths of the Bragg lines increase, and their intensities decrease rapidly. By employing the Williamson–Hall analysis of the linewidths, the observed changes above P > PC can be interpreted as due to rapidly increasing strain together with a decrease in the effective micro-crystallite size D. However, at this critical pressure, the hydrostatic conditions change due to the solidification of the PTM. The observed significant effects on the broadening of the Bragg lines and their rapid intensity reduction, together with an increasing trend seen in the lattice parameter, may be due to interstitial defects produced by shear stress (as a result of non-hydrostaticity) present for P > PC with the parameter D reflecting mean defect-free distance.