You can use the execute at begin axis key to sneak another \pgfplotsset command into the axis options. This \pgfplotsset command will be executed after the other axis options have been set:
\documentclass[12pt,a4paper,tikz]{standalone} \usepackage[T1]{fontenc} \usepackage[utf8]{inputenc} \usepackage{lmodern} \usepackage{tikz,pgfplots,grffile,amsmath} \pgfplotsset{compat=newest} \pgfplotsset{ mytikzstyle/.style={ every axis/.append style={ execute at begin axis={ \pgfplotsset{ legend style={ font=\tiny }, every x tick label/.append style={font=\scriptsize}, every y tick label/.append style={font=\scriptsize} } } } } } \pgfplotsset{mytikzstyle} \pgfplotsset{/pgfplots/width=8cm} \pgfplotsset{/pgfplots/height=6cm} \begin{document} \begin{tikzpicture} \begin{axis}[% separate axis lines, every x tick label/.append style={font=\color{black}}, legend style={at={(0.99,0.01)}, anchor=south east, legend cell align=left, align=left, draw=gray}, ] \addplot [line width=0.8pt, color=black] table[row sep=crcr]{% 1 1\\ 100 100\\ }; \addlegendentry{Hello $U_{1}\frac{xyz}{xyz}$} \end{axis} \end{tikzpicture}% \end{document}