Over the past decades, many scholars have been studying the pore volume compressibility (PVC) of porous media. However, the fundamental controls on PVC of porous media are not yet definitive. Some scholars suggest a negative correlation between PVC and initial porosity, while others suggest a positive correlation. Motivated by this discrepancy, this paper presents a new analytical model to study the PVC of fractal porous media. The predictions are compared with test results and thereby validated to be accurate. In our attempt not only to complement but also to extend the capability beyond available models, the derived model accounts for multiple fundamental variables, such as the microstructural parameters and rock lithology of porous media. Results suggest that, there is a negative correlation between PVC and initial porosity, if all other parameters are fixed, the relationship between initial porosity and PVC is not monotonic. In addition, PVC decreases with rougher pore surfaces and smaller initial minimum pore radius. Besides providing theoretical foundations for quantifying PVC of porous media, this analytical model could be applied to estimate pore structure parameters of porous media using inverse modeling.