We studied the changes in the activity of the enzymes polyphenol oxidase (PPO) and peroxidase (POX), the concentration of total soluble phenolic compounds and soluble protein content in different tobacco cultivars (Virginia and Burley) during curing. The curing procedure was a special combination of open-air-curing and flue-curing methods and a long fermentation period. In the curing period the changes in data suggested a combination of the biochemical processes and the direct effect of oxygen. A slight increase then a decrease in the concentrations of both total soluble phenolic compounds and the soluble protein content were detected. In this period we found no correlation between the concentration of total soluble phenolic compounds, the decreasing PPO and the increasing POX activity. In the fermentation period a deactivation of the enzymes (PPO and POX) and a decrease in the concentration of both total soluble phenolic compounds and soluble protein content were found, because the fermentation is not a biochemically-regulated process. Moreover, these results suggest that the end of curing period is the most favourable time for protein isolation from different tobacco cultivars