Aromatic carboxylic acids were investigated for anti-wrinkle finishing on cotton fabrics as it caused less damage to fibers. However, its application was limited to its poor water solubility. In this study, pyromellitic acid (PMA) was applied for anti-wrinkle finishing on fabric in 30%(w/w) ethanol solution instead of water. The optimum process parameters, such as concentration, bath pH, catalyst dosage, curing condition, were analyzed by orthogonal test for crosslinking cellulose. The surface morphology changes of treated fibers were recorded by scanning electron microscope (SEM). The possible reactive mechanism between PMA and cellulose was discussed by means of Fourier transform infrared spectroscopy (FTIR), thermogravimetric analyses (TGA), in-situ temperature-dependent Fourier transform infrared spectroscopy (FTIR). The results demonstrated that the optimized process for PMA crosslinking cellulose was PMA 0.3 mol/L, bath pH 1.5, sodium hypophosphite (SHP, NaH2PO2) 0.10 mol/L, baking condition 180 °C*1.5 min. The bath pH and curing temperature were the primary factors for fabric wrinkle resistance and strength lose, respectively. After repeated laundering, the strength loss of treated samples with PMA was obviously lower than that of aliphatic carboxylic acid and dimethylol dihydroxy ethylene urea (DMDHEU, 2 D resin). Meanwhile, PMA had less effect on fiber surface morphology and the fiber strength lose was mainly from the damage accumulation of macromolecular chains in fibers. The SHP catalytic action in PMA was much lower than that in aliphatic carboxylic acids for esterification. Moreover, the ortho carboxylic groups on PMA not only esterified with cellulose directly, but also dehydrated into anhydride and further reacted with cellulose. The crosslinking between PMA and cellulose was mainly by direct esterification rather than indirect esterification by anhydride intermediate. The results provided new insights for the application of insoluble crosslinker on cellulose.