$\newcommand{\Om}{\Omega} $The answer is yes, and it is even true that in your conditions \begin{equation*} I:=\int_{\Omega} \frac{f(x)^2}{(x_1-x_2)^2} \ dx_1 \ dx_2 \le C \|\nabla f \|^2_{L^2}\tag{1}\label{1} \end{equation*} Indeed, using the substitution $x_1-x_2=u$ and $x_1+x_2=v$ and doing some rescaling, reduce \eqref{1} to \begin{equation*} \int_0^1 \frac{g(u)^2}{u^2}\,du\le C_1 \int_0^1 g'(u)^2\,du \tag{2}\label{2} \end{equation*} for some universal real constant $C_1>0$ and all smooth $g$ with $g(0)=0$. But \eqref{2} is a special case of [Hardy's inequality][1], with $p=2$, so that \eqref{2} holds with $C_1=4$. --- **Details on the reduction of \eqref{1} to\eqref{2}:** By rescaling, without loss of generality $L=1/2$. Let $F(u,v):=f(\frac{u+v}2,\frac{u-v}2)$ for $(u,v)\in U(\Om)\subseteq[-1,1]^2=S$, where $U(x_1,x_2):=(x_1-x_2,x_1+x_2)$, so that $f(x)=f(x_1,x_2)=F(x_1-x_2,x_1+x_2)$ for $x\in\Om$. Extend $F$ by $0$ to the function on $S$, which will be denoted still by $F$. Then \begin{equation*} 2I=\int_{-1}^1 dv\,\int_{-1}^1 du\, \frac{F(u,v)^2}{u^2} =I_+ +I_-, \end{equation*} where \begin{equation*} I_{\pm}:=\int_{-1}^1 dv\,\int_{-1}^1 du\, \frac{F(u,v)^2}{u^2}\,1(\pm u>0). \end{equation*} Letting $F_u$ denote the partial derivative of $F$ wrt $u$, using \eqref{2} with $C_1=4$, and noting that $F_u(u,v)^2\le|\nabla f(\frac{u+v}2,\frac{u-v}2)|^2$, we get \begin{equation*} I_+\le4\int_{-1}^1 dv\,\int_0^1 du\, F_u(u,v)^2 \\ \le4\int_{-1}^1 dv\,\int_0^1 du\, |\nabla f(\tfrac{u+v}2,\tfrac{u-v}2)|^2. \end{equation*} Similarly, \begin{equation*} I_- \le4\int_{-1}^1 dv\,\int_{-1}^0 du\, |\nabla f(\tfrac{u+v}2,\tfrac{u-v}2)|^2, \end{equation*} so that \begin{equation*} I\le2\int_{-1}^1 dv\,\int_{-1}^1 du\, |\nabla f(\tfrac{u+v}2,\tfrac{u-v}2)|^2 \\ =4\int_{\Om}|\nabla f|^2 =4\|\nabla f \|^2_{L^2}. \end{equation*} So, \eqref{1} holds with $C=4$ (for $L=1/2$) $\quad\Box$. [1]: https://en.wikipedia.org/wiki/Hardy%27s_inequality