Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sodium salicylate, aspirin and indomethacin have been reported to activate the heat shock transcription factor (HSF) without enhancing the expression of the heat shock proteins (HSPs). We investigated the effects of NSAIDs on the heat shock-induced HSP expression in fish cell line CHSE-214. Here we reveal that in CHSE-214 cells, co-exposure to sodium salicylate/aspirin and heat shock (24°C) enhances and prolongs the heat shock-induced HSP70 expression presumably through activation of the HSF. In contrast, the heat shock-induced HSP90 expression was inhibited by these NSAIDs. Thus, sodium salicylate and aspirin are likely to exert different effects on the heat shock-induced HSP70 and HSP90 expression. Indomethacin, another cyclooxygenase inhibitor, had no stimulatory or inhibitory effects on the heat shock-induced HSP70 and 90 expression, thereby indicating that sodium salicylate and aspirin may modulate the heat shock response via pathways not involving cyclooxygenase. Since anti-oxidants could inhibit the heat shock-induced HSP70 expression, the stimulatory effects of sodium salicylate and aspirin on the HSP70 expression are not likely due to their ability to act as anti-oxidants. Additionally, sodium salicylate and aspirin could exert synergistic effects on the HSP70 expression at lower temperatures (20–22°C) that did not induce the HSP70 expression.