Spider-Man's spider-sense is usually described as a tingling sensation he gets when in danger, non-specific about the nature of the danger but able to identify its direction.

Marvel.com states:

His spider-sense provides an early warning detection system linked with his superhuman kinesthetics, enabling him the ability to evade most any injury, provided he doesn't cognitively override the autonomic reflexes.

Spider-Man wikia says about it's nature:

Several Spider Powered individuals have a "Spider-sense" which is a metacognative ability that warns them of impending danger.

So, we know about how it functions but I don't know about the nature of the spider-sense. Is it a supernatural or psychic sense (as the metacognitive quote seems to imply)? Is it, like the other powers, based on spider genetics (and if so is there any physiological insight about how it works)?

I don't know much about the comics but I guess the explanation can change with time, I'd prefer the current incarnation.

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    It's a subconscious response to perceived danger. His nervous system and brain are modified by the spider that bit him to the point that he can subconsciously interpret/perceive those sensations and recognize an imminent threat to his person or group. – Derek Nov 9 '17 at 4:00
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    Just good common spider-sense. – Paul D. Waite Nov 9 '17 at 9:49
  • I think at least in the comics we can find many many cases that are only explainable with a kind of split second precognition (like Jedi reflexes). – Hothie Nov 9 '17 at 10:53
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    It's a non-sense. – user46249 Nov 9 '17 at 17:57
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    The tingly kind. (As opposed to the jiggly kind, I guess.) – Harry Johnston Nov 9 '17 at 19:00

It may be both supernatural and science based

Hints about how it works physically include:

  • Ability to sense radiofrequency. That's how spider-tracers work, the spider-sense picks up a special wavelength. enter image description here

  • Somehow tied to DNA. Clones of Peter, sporting the same DNA, cannot detect each other. Neither can he detect a symbiote that previously fused with him.* enter image description here

  • Possible origin in Spiders physiology. Author's may have noticed spider are higly apt at evading danger, One important source of information about the world and its hazards comes from highly sensitive hairs that cover the bodies of most spiders and perceive low-level vibrations. This Because science video greatly ilustrates how incredibly sensitive spiders can be, to the point of almost completely explaining how it may look like precognition:

However some comics point to more mystical nature. While spiders don't have psychic powers [citation needed], the marvel universe features the Web of Life and Destiny and the spider sense is explained (Amazing Spider-man Vol.3 Issue 15) as feeling through the strings of this web.

Scene from Amazing Spider-man Vol.3 Issue 15

Ultimately, during his encounters with Ezekiel, Peter accepts that both explanations to his powers (spider bite and web of destiny) may be true like two faces of the same coin.

(*) Although, as remarked in this answer, another explanation for the symbiote not triggering spider-sense consist on the alien costume canceling out spider-sense by projecting brain waves frequencies upon Spider-Man. That's consistent with the radiofrequency theory.

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