The catalytic performance of vanadium incorporated MCM-41 catalysts for the partial direct oxidation of methane to formaldehyde was previously investigated. The laboratory controllable factors, i.e., reaction temperature, V-loading, gas hourly space velocity, reactant ratio (CH4:O2), and reaction pressure, were observed to significantly affect the formaldehyde selectivity, methane conversion, and formaldehyde space time yield. As a simplified approach to optimize the production of formaldehyde, this paper illustrates the novel application of statistical multivariate analysis and prediction through a multi-regression model, as well as the optimization of the processing parameters in the complex reaction process. This approach is advantageous, especially when experimental evaluation and optimization of a process is time consuming and expensive. By carrying out a finite number of experiments, statistical modeling in this work shows reasonable good prediction ability. Moreover, not only are the synergistic effects between reaction parameters revealed, but also a comprehensive understanding of the whole production process over variation of the all reaction parameters (within the phase space represented by the experimental grid) are allowed.