Lysosomal integrity in mussels is widely used as a biomarker in coastal environments to demonstrate exposure to trace organic pollutants. However, few studies have determined the long-term influences of seasonal variations on the bioaccumulation of trace organics and subsequently altered response of lysosomal integrity in mussels. This study aimed to test three null hypotheses that (1) bioaccumulations of total polycyclic aromatic hydrocarbon (SigmaPAH) and (2) total polychlorinated biphenyl (SigmaPCB), and (3) lysosomal integrity as indicated by Neutral Red retention time (NRRT) in haemocytes, in the green-lipped mussel Perna viridis were not seasonally dependent. The tissue concentrations of SigmaPAH and SigmaPCB and haemocytic NRRT were determined in P. viridis in a metropolitan harbour, subtropical Hong Kong during the wet and dry seasons from 2004 to 2007. Additional information on temperature, salinity, dissolved oxygen and total ammonia nitrogen in seawater, and sediment levels of SigmaPAH and SigmaPCB, were extracted from published data and re-analyzed. Our results accepted all null hypotheses, based on the minimal seasonal influences of seawater temperature and salinity on all studied parameters, in which no significant differences between the wet and dry seasons were detected. The seasonal effect was likely outweighed by the greatly improved water quality and pollution abatement noted inside the harbour, with a gradual shift in mussel PAHs from a pyrolytic origin to a petrogenic origin. Spatially, the site east of the harbour was relatively unpolluted. The single use of NRRT in P. viridis explained 25% of the total variation of the integrated pollution patterns in seawater, sediments and mussels. The present study suggested that the dynamic change of trace organics could be reflected by the response on lysosomal integrity in P. viridis, which was recommended as a routine screening biomarker in monitoring of harbour water quality across seasons.