The reuse and regeneration of HZSM-5 zeolite in the catalytic co-pyrolysis of corn stover/high-density polyethylene was investigated using a tube reactor. The effect of acid washing treatment of corn stover on the catalytic activities of HZSM-5 zeolite was studied. The composition of the obtained bio-oil was analyzed by GC-MS, and the properties of fresh, spent, and regenerated HZSM-5 catalysts were measured using TG, ICP-MS, SEM/EDS, BET, and NH3-TPD, respectively. The results showed that aromatics were the main products for the catalytic co-pyrolysis of corn stover/high-density polyethylene with fresh HZSM-5. With the increase of HZSM-5 reuse times, the yield of aromatics decreased gradually, and the BET area, pore volume, and acidity of the catalyst decreased sharply, indicating the reduced catalytic activities of HZSM-5. The acid washing pretreatment of corn stover enhanced the formation of oxygen-containing intermediates, which accelerated the deactivation of HZSM-5 zeolite. The catalytic activity of the regenerated HZSM-5 over acid washing corn stover/high-density polyethylene was recovered, while the catalytic activity of the regenerated HZSM-5 over raw corn stover/high-density polyethylene was slightly lower than that of fresh HZSM-5. This was due to the fact that alkali/alkaline earth metals were significantly accumulated over the HZSM-5 catalyst, which couldn’t be removed by calcination and thus could deposit on the strong acid sites, causing the “poisoning” deactivation of the catalyst. The above results suggest that the deactivation of HZSM-5 caused by coke can be regenerated by calcination, while that caused by alkali/alkaline earth metals is difficult to recover. The acid-washing pretreatment can effectively eliminate the effect of alkali/alkaline earth metals, which is beneficial to prolong the lifetime of the catalyst.