A study has been carried out on the effect of operating conditions (bio-oil/methanol ratio in the feed, temperature) on the deactivation of HZSM-5 catalysts used in the production of hydrocarbons by catalytic conversion of crude bio-oil continuously fed into a fluidized bed reactor. The bio-oil to be fed into the reactor has previously been subjected to an on-line thermal transformation in which the pyrolytic lignin derivatives have been re-polymerized. The coke deposited on the catalyst has been studied using different analytical techniques (FTIR spectroscopy, MS/FTIR-TPO, 13C CP-MAS NMR spectroscopy). The results evidence a direct relationship between coke deposition and deactivation and the concentration of bio-oil oxygenates in the reaction medium. Consequently, bio-oil conversion should be promoted in order to mitigate coke deposition. This is achieved using a HZSM-5 zeolite catalyst with a reduced SiO2/Al2O3 ratio and increasing reaction temperature and methanol/bio-oil ratio in the feed. The acidity of the HZSM-5 zeolite also has an influence on the nature of the coke, given that it contributes to increasing coke condensation towards polycondensed aromatic structures, although this has a minor effect on bio-oil conversion decrease with time on stream. The results obtained evidence the interest of the initiatives for co-feeding bio-oil with methanol to obtain hydrocarbons.