621 · proper noun1
The website name is a clipping of e621, using only the numbers in the name of the website. The website itself is from E621 (the E number for monosodium glutamate when used as a flavor enhancer) as an indirect reference to the service's content being tasty (“sexually appealing”). Compare the name of e621's work-safe mirror website, e926, which matches E926 (E number for the bleaching agent chlorine dioxide), perhaps as a reference to figurative eye bleach. The day is a direct reference to the website and based on 6/21, an abbreviation in the United States for 21 June.
621 · noun2
A shortening.
Etymology from Wiktionary, CC BY-SA 4.0.