In this paper, we have studied the separation for the biharmonic Laplace-Beltrami differential operator
\begin{equation*}Au(x)=-\Delta \Delta u(x)+V(x)u(x),\end{equation*}
for all $x\in R^{n}$, in the Hilbert space $H=L_{2}(R^{n},H_{1})$ with the operator potential $V(x)\in C^{1}(R^{n},L(H_{1}))$, where $L(H_{1})$ is the space of all bounded linear operators on the Hilbert space $H_{1}$, while $\Delta \Delta u$\ is the biharmonic differential operator and
\begin{equation*}\Delta u{=-}\sum_{i,j=1}^{n}\frac{1}{\sqrt{\det g}}\frac{\partial }{{\partial x_{i}}}\left[ \sqrt{\det g}g^{-1}(x)\frac{\partial u}{{\partial x}_{j}}\right]\end{equation*}
is the Laplace-Beltrami differential operator in $R^{n}$. Here $g(x)=(g_{ij}(x))$ is the Riemannian matrix, while $g^{-1}(x)$ is the inverse of the matrix $g(x)$. Moreover, we have studied the existence and uniqueness Theorem for the solution of the non-homogeneous biharmonic Laplace-Beltrami differential equation $Au=-\Delta \Delta u+V(x)u(x)=f(x)$ in the Hilbert space $H$ where $f(x)\in H$ as an application of the separation approach.