The seasonal variations in biochemical composition and reproductive activity of the venus clam Cyclina sinensis (Gmelin) from the Yellow River delta in China were investigated from April 2007 to March 2008 in relation to environmental factors. According to histological observations, gametogenesis began in January when the water temperature was low. Gametes matured mainly in June and July when the condition index (CI) and mean oocyte diameter peaked. Spawning occurred primarily in August when the temperature was highest, and coincided with phytoplankton bloom. The CI and oocyte diameter decreased sharply after spawning occurred, as mostly larger, mature gametes have been released. In autumn, the plentiful phytoplankton and higher water temperature were fit for the larvae to grow. Biochemical analysis indicated that gametogenesis took place at the expense of reserves accumulated in the various tissues previously during winter. A slight increase in lipid and protein content in female gonad—visceral mass during sexual maturation was observed, demonstrating that lipid and protein would be accumulated as vitellin in oocytes. Conversely, the lipid and protein content in the male gonad—visceral mass decreased during sexual maturation. The biochemical compositions in the adductor muscle and mantle varied during the study period, suggesting that they could support reproduction and growth. Seasonal variation in the RNA-to-DNA ratio suggests that it cannot reflect the situation of gonad development in this species.