Sicyos hillebrandii is a climbing annual herb. The stems can grow several meters long and are initially scabrous before becoming glabrate. The leaves are simple and alternate, with broadly reniform blades with a broad basal sinus. The blades measure 10–12 cm long and 10–13 cm wide and are shallow to deeply palmately 5–9-lobed. The lobes are narrowly triangular to narrowly ovate or obovate. The leaf apex is acute and mucronate. The surfaces are hispid, with the upper surface being sparsely so. The margins are dentate or lobulate, and the petioles are 3–7 cm long. Stipules are absent, and tendrils in the stipular position are 3–4-branched. The flowers are unisexual, with the plants being monoecious or dioecious and actinomorphic (radially symmetric). Staminate flowers are arranged in panicles on peduncles 10–18 cm long and subglabrous, with glandular-pubescent pedicels. Pistillate flowers are arranged in heads of 20–30; sessile on 1.2–2.6 cm long peduncles. The calyx has five sepals inserted into the hypanthium. The corolla of staminate flowers is greenish white, 5-lobed, 3–6 mm in diameter, with petals inserted on the hypanthium alternate with calyx lobes, usually connate at the base, and the limb often rotate. The corolla of pistillate flowers is also 5-lobed, but the perianth is usually smaller than in staminate flowers. Staminate flowers have 2–3(–5) stamens inserted at the base of the hypanthium, with filaments connate into a column and anthers that are curved or flexuous, coherent, and twisted in a head, opening by longitudinal slits. Pistillate flowers lack staminodes. The ovary is inferior, composed of a single carpel or 3-carpellate with carpels connate into a single 3-lobed cell, with one ovule and parietal placentation. The stigma is capitate. The fruit is brown and fusiform, measuring 10–12 mm long and 5–7 mm in diameter. It is compressed or angled at the base, puberulent, long-beaked, and indehiscent. Each fruit contains one ovate seed, which lacks endosperm.