New cases of COVID-19 increased rapidly and brought challenges to human health in Yantai after China adjusted the dynamic COVID-zero strategy at the end of 2022. To monitor the evolutionary process and characterize variants circulating in Yantai in 2023, 613 nasopharyngeal swab samples from confirmed COVID-19 patients were sequenced, assigned lineages, construct phylogenetic tree and analyzed mutations located in S-protein. The results showed that most of sequences belonged to 10 lineages. Among these, 20.65%(127/613) were identified as BF.7.14, 20.98% (129/613) as EG, 13.98% (86/613) as HK, 12.36%(76/613) as DY, 8.32%(51/613) as XBB.1, 8.32% (51/613) as FL, 3.41%(21/613) as BA.5.2, 1.79%(11/613) as BN.1, 1.79%(11/613) as FY.3 and 0.65% as DZ.1 (4/613). Variants derived BA.5 prevailed from Jan to April and variants derived XBB were dominant in second half year. The prevalent variants were the same as the SARS-CoV-2 variants circulating in China at the same time. The S-protein of prevalent variants shared 29 mutations and specific mutations were present in different variants. The mutations of S-protein gradually accumulated and augmented transmissibility and immune escape of variants. New variants with higher viral fitness appeared continuously and brought challenges to human health, so long-term genomic surveillance of SARS-CoV-2 is still necessary in the future.