First, you will need to have a professionally polished manuscript. Publishers receive hundreds to thousands of manuscripts daily. In order for yours to get more than just a passing glance, it will need to be:
1) Properly formatted. Traditional formatting would consist of 1-inch margins all around, 12-point font (typically Courier or Times New Roman), and double-spaced.
2) Grammatically correct and error-free. Your work needs to be as clean as possible.
3) Printed on white paper, free of stains or wrinkles.
Craft a synopsis. A synopsis is a shortened version of the story, a breakdown of the story from beginning to end. It should be no longer than three pages and always provide the ending.
Again, the synopsis needs to be top quality, error-free and properly formatted.
Include a cover letter with your submission package to the publisher. In the letter you should include your contact information, a very brief blurb (one to two sentences) about the story, the genre your book fits into and a list of any professional writing credits you may have. Always make certain to address the letter to the specific editor by their name. Do not write, "Dear Editor," as it is a surefire way to get rejected before they even look at your work.
Generate a list of publishers. Most writers suggest checking within the pages of books you've read that are similar to the one you've written. There are printed market guides that come out annually; however, submission information is only as current as when the book was printed. Always double-check to make certain they are still a viable publisher and still accepting manuscripts before sending yours off to them.
A terrific resource online is Doutrope. http://www.duotrope.com/index.aspx. This online resource allows you to search by genre, word count, publisher type and several other ways. Doutrope is updated daily, so you can be certain you are receiving the most current information about any given publisher.
It is very important that you only send your work to publishers who are:
1) Open for submissions
2) Taking unsolicited manuscripts. Meaning, they allow authors to send their work without knowing anything about the author or work in advance. A solicited manuscript is one that the publisher specifically requests the novel from either the author or agent. Many large New York publishers do not take unsolicited manuscripts.
3) Accepting manuscripts in your genre.
Some publishers accept electronic submissions (via email), while others require a hard submission (via standard mail).
Ensure your submission fits the publisher's guidelines. These will include:
1) If they are open for unsolicited submissions.
2) If they accept electronic or hard copy submissions, and details on who, how, where and what to send.
3) The specific genres they accept.
4) Some may include turnaround time or information such as non-response, which is the equivalent of a rejection.