The present technology relates to a signal processing apparatus, a signal processing method, a program, and a signal transmission system realizing an SDI (serial digital interface) capable of effectively transmitting an audio stream together with video data, for example, of which the frame rate is 100 Hz or 120 Hz. An audio multiplexing unit multiplexes an audio sample into a data area of horizontal lines of n2 (here, 2≦n2≦n1) rows after a first horizontal line in which the audio sample is generated, which is a predetermined data area arranged within a horizontal blanking area disposed for each horizontal line of video data in a data stream defined in a format of an SDI used for transmitting the video data, in a case where an audio is sampled at an interval of once or less for horizontal lines of n1 (here, n1≧2) rows of the video data of a predetermined frame rate. For example, the present technology can be applied to a broadcast camera.